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Sample records for therapeutically relevant concentrations

  1. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Directory of Open Access Journals (Sweden)

    Danbo Yang

    2010-12-01

    Full Text Available The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(L-g-glutamylglutamine-paclitaxel nano-conjugate (PGG-PTX. PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  2. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    International Nuclear Information System (INIS)

    Yang, Danbo; Yu, Lei; Van, Sang

    2010-01-01

    The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic

  3. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Danbo [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Yu, Lei, E-mail: yu-lei@gg.nitto.co.jp [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States); Van, Sang [Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States)

    2010-12-23

    The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  4. Initial diagnosis of therapeutically relevant thoracic lesions in polytraumatised patients

    International Nuclear Information System (INIS)

    Danz, B.; Biehl, C.; Baehren, W.

    1996-01-01

    To determine the value of supine chest radiography in comparison to orientating chest CT in the initial diagnostic evaluation of severely polytraumatised patients. 303 patients with primary indication for a cranial CT following trauma were investigated between 1988 and 1993. After performing the cranial CT all patients underwent a chest CT with an average of 6 CT slices without changing the position of the patient and with a median scan time of 4 minutes. The results of the chest CT were correlated with the findings of the supine chest radiography in regard to therapeutically relevant pathological changes. The sensitivity in detection of pneumothorax in supine chest radiography was 53% versus 97% in CT, atelectasis 20% versus 94%, lung contusion 79% versus 99%, haemotothorax 62% versus 97%. More fractures were found conventionally (sensitivity 94%) than by chest CT (sensitivity 44%). Supine chest radiography of polytraumatised patients is clearly inferior to orientating chest CT in demonstrating posttraumatic lesions; obtaining therapeutically relevant information justifies the additionally needed small amount of time. (orig.) [de

  5. Therapeutic relevance of penicillin-induced hypersensitivity of Staphylococcus aureus to killing by polymorphonuclear leukocytes.

    OpenAIRE

    Lam, C; Georgopoulos, A; Laber, G; Schütze, E

    1984-01-01

    There is an overwhelming body of evidence that certain Staphylococcus aureus strains become more sensitive to killing by polymorphonuclear leukocytes after their growth in media containing subinhibitory concentrations of penicillin. However, it is not clear to what extent this phenomenon contributes to the curative effect of penicillin in vivo. To explore its therapeutic relevance, we evaluated the interaction of staphylococci pretreated with penicillin in vitro with leukocytes in cell-proof ...

  6. Radon concentration measurements in therapeutic spring water

    International Nuclear Information System (INIS)

    Deak, N.; Horvath, A.; Sajo B, L.; Marx, G.

    1996-01-01

    It is believed that people undergoing a curative cycle in a given spa, may receive a dose in the range of 400 mSv/year which is many times the average annual dose so that their risk of lung cancer may increase by 3% or more. To determine the risk due to the natural radioactivity, of the most frequented spas in Budapest (H), we selected four and some others located on the country side being of particular interest. Results of the radon concentration in spring water are presented, with the evidence that some spas have a high radon concentration. We conclude that patients receiving treatment may be exposed to an additional dose in the range of 29-76 mSv/year that at the bronchia could be between 445-1182 mSv/year. (authors). 6 refs., 2 figs., 2 tabs

  7. Interleukin-6 in Schizophrenia—Is There a Therapeutic Relevance?

    Directory of Open Access Journals (Sweden)

    Milica Milovan Borovcanin

    2017-11-01

    Full Text Available Renewing interest in immune aspects of schizophrenia and new findings about the brain-fat axis encourage us to discuss the possible role of interleukin-6 (IL-6 in schizophrenia. Previously, it was suggested that a primary alteration of the innate immune system may be relevant in schizophrenia. Functional dichotomy of IL-6 suggests that this chemical messenger may be responsible for regulating the balance between pro- and anti-inflammatory responses, with tissue-specific properties at the periphery and in the central nervous system. Specific phase of this chronic and deteriorating disorder must be considered, which can involve IL-6 in acute or possible chronic inflammation and/or autoimmunity. We give an overview of IL-6 role in the onset and progression of this disorder, also considering cognitive impairment and metabolic changes in patients with schizophrenia. Data suggest that decreased serum level of IL-6 following antipsychotic therapy could be predisposing factor for the development of obesity and obesity-related metabolic disorders in schizophrenia. As we reviewed, the IL-6 plays significant role in disease genesis and progression, so the use of specific inhibitors may not only be beneficial for exacerbation and alleviation of positive symptoms, but may attenuate cognitive impairment in patients with schizophrenia.

  8. Paracetamol (acetaminophen) protein adduct concentrations during therapeutic dosing.

    Science.gov (United States)

    Heard, Kennon; Green, Jody L; Anderson, Victoria; Bucher-Bartelson, Becki; Dart, Richard C

    2016-03-01

    Paracetamol protein adducts (PPA) are a biomarker of paracetamol exposure. PPA are quantified as paracetamol-cysteine (APAP-CYS), and concentrations above 1.1 μmol l(-1) have been suggested as a marker of paracetamol-induced hepatotoxicity. However, there is little information on the range of concentrations observed during prolonged therapeutic dosing. The aim of the present study was to describe the concentration of PPA in the serum of subjects taking therapeutic doses of paracetamol for at least 16 days. Preplanned secondary aim of a prospective randomized controlled (placebo vs. 4g day(-1) paracetamol) trial. We measured subjects' serum PPA concentrations every 3 days for a minimum of 16 days. We also measured concentrations on study days 1-3 and 16-25 in subsets of patients. PPA were quantified as APAP-CYS after gel filtration and protein digestion using liquid chromatography/mass spectrometry. Ninety per cent of subjects had detectable PPA after five doses. Median APAP-CYS concentrations in paracetamol-treated subjects increased to a plateau of 0.1 μmol l(-1) on day 7, where they remained. The highest concentration measured was 1.1 μmol l(-1) and two subjects never had detectable PPA levels. PPA were detected in the serum of 78% of subjects 9 days after their final dose. PPA are detectable in the vast majority of subjects taking therapeutic doses of paracetamol. While most have concentrations well below the threshold associated with hepatotoxicity, concentrations may approach 1.1 μmol l(-1) in rare cases. Adducts are detectable after a few doses and can persist for over a week after dosing is stopped. © 2015 The British Pharmacological Society.

  9. Concentration of 188Re-Perrhenate for Therapeutic Radiopharmaceuticals

    International Nuclear Information System (INIS)

    Bokhari, T.H.; Hina, S.; Ahmad, M.; Iqbal, M.

    2013-01-01

    Summary: Rhenium-188 (T1/2=16.9h) has great potential for a variety of therapeutic applications, including radionuclide synovectomy, oncology and bone pain palliation. The radioactive concentration of 188Re is dependent upon the specific activity of 188W, which dictates the bed size of the alumina/gel column. Due to the high content of inactive tungsten in neutron irradiated WO3, large columns containing aluminum oxide or gel are needed to prepare to double neutron capture based 188W/188Re generators that results in large elution volumes containing relatively high188W contents and low concentrations of /sup 188/ ReO/sub 4/ This decrease in specific volume of 188ReO/sub 4/ places a limitation because a high radioactive concentration of 188ReO4 - is always needed for filling angioplasty balloons or other therapeutic radiopharmaceuticals like188Re -EHDP 188Re -EDTMP, 188Re - MAG3 and 188Re -DTPA. We report post elution concentration of 188ReO4 - using in- house prepared lead cation exchange and alumina columns. Using these columns high bolus volume (10 mL saline) of 188ReO4 - can conveniently be concentrated in 1 mL of physiological saline for therapeutic use. (author)

  10. A pragmatic definition of therapeutic synergy suitable for clinically relevant in vitro multicompound analyses.

    Science.gov (United States)

    Kashif, Muhammad; Andersson, Claes; Åberg, Magnus; Nygren, Peter; Sjöblom, Tobias; Hammerling, Ulf; Larsson, Rolf; Gustafsson, Mats G

    2014-07-01

    For decades, the standard procedure when screening for candidate anticancer drug combinations has been to search for synergy, defined as any positive deviation from trivial cases like when the drugs are regarded as diluted versions of each other (Loewe additivity), independent actions (Bliss independence), or no interaction terms in a response surface model (no interaction). Here, we show that this kind of conventional synergy analysis may be completely misleading when the goal is to detect if there is a promising in vitro therapeutic window. Motivated by this result, and the fact that a drug combination offering a promising therapeutic window seldom is interesting if one of its constituent drugs can provide the same window alone, the largely overlooked concept of therapeutic synergy (TS) is reintroduced. In vitro TS is said to occur when the largest therapeutic window obtained by the best drug combination cannot be achieved by any single drug within the concentration range studied. Using this definition of TS, we introduce a procedure that enables its use in modern massively parallel experiments supported by a statistical omnibus test for TS designed to avoid the multiple testing problem. Finally, we suggest how one may perform TS analysis, via computational predictions of the reference cell responses, when only the target cell responses are available. In conclusion, the conventional error-prone search for promising drug combinations may be improved by replacing conventional (toxicology-rooted) synergy analysis with an analysis focused on (clinically motivated) TS. ©2014 American Association for Cancer Research.

  11. Colonization, Pathogenicity, Host Susceptibility and Therapeutics for Staphylococcus aureus: What is the Clinical Relevance?1

    Science.gov (United States)

    Tong, Steven Y.C.; Chen, Luke F.; Fowler, Vance G.

    2011-01-01

    Staphylococcus aureus is a human commensal that can also cause a broad spectrum of clinical disease. Factors associated with clinical disease are myriad and dynamic and include pathogen virulence, antimicrobial resistance and host susceptibility. Additionally, infection control measures aimed at the environmental niches of S. aureus and therapeutic advances continue to impact upon the incidence and outcomes of staphylococcal infections. This review article focuses on the clinical relevance of advances in our understanding of staphylococcal colonization, virulence, host susceptibility and therapeutics. Over the past decade key developments have arisen. First, rates of nosocomial methicillin-resistant S. aureus (MRSA) infections have significantly declined in many countries. Second, we have made great strides in our understanding of the molecular pathogenesis of S. aureus in general and community-associated MRSA in particular. Third, host risk factors for invasive staphylococcal infections, such as advancing age, increasing numbers of invasive medical interventions, and a growing proportion of patients with healthcare contact, remain dynamic. Finally, several new antimicrobial agents active against MRSA have become available for clinical use. Humans and S. aureus co-exist and the dynamic interface between host, pathogen and our attempts to influence these interactions will continue to rapidly change. Although progress has been made in the past decade, we are likely to face further surprises such as the recent waves of community-associated MRSA. PMID:22160374

  12. Transport of Fluorescently Labeled Hydroxyapatite Nanoparticles in Saturated Granular Media at Environmentally Relevant Concentrations of Surfactants

    Science.gov (United States)

    Little is known about the mobility of engineered nanoparticles (ENPs) in granular media at environmentally relevant concentration of surfactant, which represents a critical knowledge gap in employing ENPs for in-situ remediation of contaminated groundwater. In this study, transpo...

  13. CT-guided biopsy: diagnostic relevance, therapeutic consequences and economic aspects

    International Nuclear Information System (INIS)

    Schwarzenberg, H.; Mueller-Huelsbeck, S.; Link, J.; Brossmann, J.; Fahl, M.; Quirin, A.; Heller, M.

    1996-01-01

    Purpose: To evaluate the diagnostic and clinical relevance and therapeutic consequences of CT-guided biopsy with regard to economic aspects. Methods: 213 CT-guided biopsies in 190 were evaluated. All information regarding patient referral, reason for request, body region, underlying diagnosis, and clinical consequences were registered over a period of 22.2±9.4 month. Results: Patient referral to biopsy was mainly from the departments of surgery, internal medicine, and radiotherapy with the question of tumor and metastasis. Less than 5% of biopsies were performed in outpatients. Main regions were the lung (39%), the abdomen (35%), and the skeleton (11%). Biopsy and surgical histology corresponded in 73%. Largest diagnosis groups were benign unspecific tissues or other benign lesions in 24%. As a result of CTP no further procedures necessary in 22.5%. Follow-up studies or conservative treatment were indicated in 11.3%. Surgical procedures were needed in only 15.5%. There was only one complication requiring therapy. Conclusion: CT-guided biopsy is a safe procedure, which helps to avoid unnecessary cost-intensive diagnostics and surgical treatment. If CTP is performed early and in outpatients residence time in the hospital is reduced and thus money is saved. (orig.) [de

  14. Can fluconazole concentrations in saliva be used for therapeutic drug monitoring?

    NARCIS (Netherlands)

    Koks, C. H.; Crommentuyn, K. M.; Hoetelmans, R. M.; Mathôt, R. A.; Beijnen, J. H.

    2001-01-01

    The saliva/plasma concentration ratio of fluconazole was investigated in 22 HIV-1-infected individuals with an oropharyngeal Candida infection to determine whether saliva fluconazole concentrations could provide useful information for therapeutic drug monitoring in this population. Steady-state

  15. Assessing therapeutic relevance of biologically interesting, ampholytic substances based on their physicochemical and spectral characteristics with chemometric tools

    Science.gov (United States)

    Judycka, U.; Jagiello, K.; Bober, L.; Błażejowski, J.; Puzyn, T.

    2018-06-01

    Chemometric tools were applied to investigate the biological behaviour of ampholytic substances in relation to their physicochemical and spectral properties. Results of the Principal Component Analysis suggest that size of molecules and their electronic and spectral characteristics are the key properties required to predict therapeutic relevance of the compounds examined. These properties were used for developing the structure-activity classification model. The classification model allows assessing the therapeutic behaviour of ampholytic substances on the basis of solely values of descriptors that can be obtained computationally. Thus, the prediction is possible without necessity of carrying out time-consuming and expensive laboratory tests, which is its main advantage.

  16. Therapeutic concentrations of mitoxantrone elicit energetic imbalance in H9c2 cells as an earlier event.

    Science.gov (United States)

    Rossato, Luciana Grazziotin; Costa, Vera Marisa; Vilas-Boas, Vânia; de Lourdes Bastos, Maria; Rolo, Anabela; Palmeira, Carlos; Remião, Fernando

    2013-12-01

    Mitoxantrone (MTX) is a chemotherapeutic agent that emerged as an alternative to anthracycline therapy. However, MTX also causes late cardiotoxicity, being oxidative stress and mitochondrial-impaired function proposed as possible mechanisms. This work aimed to investigate the relevance of these mechanisms to the MTX toxicity in H9c2 cells, using therapeutic concentrations. The observed cytotoxicity of MTX was time and concentration dependent in both lactate dehydrogenase leakage assay and MTT reduction assay. Two therapeutic concentrations (100 nM and 1 μM) and three time points were selected (24, 48, and 96 h) for further studies. Both MTX concentrations caused a significant increase in caspase-3 activity, which was not prevented by inhibiting MTX CYP450-metabolism. Significant decreases were observed in the total and reduced glutathione levels only in MTX 100 nM at 96 h; however, neither alterations in oxidized glutathione nor increases in the malondialdehyde levels were observed at any time or concentrations tested. On the other hand, changes in the intracellular ATP levels, mitochondrial membrane potential, and intracellular calcium levels were observed in both concentrations and all time tested. Noteworthy, decreased levels of ATP-synthase expression and activity and increases in the reactive species generation were observed at 96 h in both working concentrations. However, the radical scavenger N-acetylcysteine or the mitochondrial function enhancer L-carnitine did not prevent MTX cytotoxicity. Thus, this work evidenced the early MTX-induced energetic crisis as a possible key factor in the cell injury.

  17. Significance of antioxidant potential of plants and its relevance to therapeutic applications.

    Science.gov (United States)

    Kasote, Deepak M; Katyare, Surendra S; Hegde, Mahabaleshwar V; Bae, Hanhong

    2015-01-01

    Oxidative stress has been identified as the root cause of the development and progression of several diseases. Supplementation of exogenous antioxidants or boosting endogenous antioxidant defenses of the body is a promising way of combating the undesirable effects of reactive oxygen species (ROS) induced oxidative damage. Plants have an innate ability to biosynthesize a wide range of non-enzymatic antioxidants capable of attenuating ROS- induced oxidative damage. Several in vitro methods have been used to screen plants for their antioxidant potential, and in most of these assays they revealed potent antioxidant activity. However, prior to confirming their in vivo therapeutic efficacy, plant antioxidants have to pass through several physiopharmacological processes. Consequently, the findings of in vitro and in vivo antioxidant potential assessment studies are not always the same. Nevertheless, the results of in vitro assays have been irrelevantly extrapolated to the therapeutic application of plant antioxidants without undertaking sufficient in vivo studies. Therefore, we have briefly reviewed the physiology and redox biology of both plants and humans to improve our understanding of plant antioxidants as therapeutic entities. The applications and limitations of antioxidant activity measurement assays were also highlighted to identify the precise path to be followed for future research in the area of plant antioxidants.

  18. Genomics and systems biology - How relevant are the developments to veterinary pharmacology, toxicology and therapeutics?

    NARCIS (Netherlands)

    Witkamp, R.F.

    2005-01-01

    This review discusses some of the recent developments in genomics and its current and future relevance for veterinary pharmacology and toxicology. With the rapid progress made in this field several new approaches in pharmacological and toxicological research have developed and drug discovery and

  19. Blood Outgrowth Endothelial Cells Increase Tumor Growth Rates and Modify Tumor Physiology: Relevance for Therapeutic Targeting

    Energy Technology Data Exchange (ETDEWEB)

    Pagan, Jonathan, E-mail: jdpagan@uams.edu; Przybyla, Beata; Jamshidi-Parsian, Azemat [Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States); Gupta, Kalpna [Vascular Biology Center and Division of Hematology-Oncology Transplantation, Department of Medicine, University of Minnesota Medical School, MN 72223 (United States); Griffin, Robert J. [Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States)

    2013-02-18

    Endothelial cell precursors from human peripheral blood have been shown to home to areas of neovascularization and may assist tumor growth by increasing or fortifying blood vessel growth. In the present study, the influence of these cells on tumor growth and physiology was investigated and the role of these cells as a therapeutic target or in determining treatment sensitivity was tested. After isolation from human blood and expansion in vitro, actively growing cells with verified endothelial phenotype (Blood Outgrowth Endothelial Cell, BOEC) were injected i.v. into tumor bearing mice for three consecutive days. The growth rate was significantly enhanced in relatively small RERF human lung tumors (i.e., less than 150 mm{sup 3}) grown in immunocompromised mice by an average of 1.5-fold while it had no effect when injections were given to animals bearing larger tumors. There were no signs of toxicity or unwanted systemic effects. We also observed evidence of increased perfusion, vessel number, response to 15 Gy radiation and oxygenation in RERF tumors of animals injected with BOECs compared to control tumors. In addition, FSaII murine fibrosarcoma tumors were found to grow faster upon injection of BOECs. When FSaII tumors were subjected to a partial thermal ablation treatment using high intensity focused ultrasound (HIFU) there was consistently elevated detection of fluorescently labeled and i.v. injected endothelial precursors in the tumor when analyzed with optical imaging and/or histological preparations. Importantly, we also observed that BOECs treated with the novel anti-angiogenic peptide anginex in-vitro, show decreased proliferation and increased sensitivity to radiation. In vivo, the normal increase in FSaII tumor growth induced by injected BOECs was blunted by the addition of anginex treatment. It appears that endothelial precursors may significantly contribute to tumor vessel growth, tumor progression and/or repair of tumor damage and may improve the

  20. Blood Outgrowth Endothelial Cells Increase Tumor Growth Rates and Modify Tumor Physiology: Relevance for Therapeutic Targeting

    International Nuclear Information System (INIS)

    Pagan, Jonathan; Przybyla, Beata; Jamshidi-Parsian, Azemat; Gupta, Kalpna; Griffin, Robert J.

    2013-01-01

    Endothelial cell precursors from human peripheral blood have been shown to home to areas of neovascularization and may assist tumor growth by increasing or fortifying blood vessel growth. In the present study, the influence of these cells on tumor growth and physiology was investigated and the role of these cells as a therapeutic target or in determining treatment sensitivity was tested. After isolation from human blood and expansion in vitro, actively growing cells with verified endothelial phenotype (Blood Outgrowth Endothelial Cell, BOEC) were injected i.v. into tumor bearing mice for three consecutive days. The growth rate was significantly enhanced in relatively small RERF human lung tumors (i.e., less than 150 mm 3 ) grown in immunocompromised mice by an average of 1.5-fold while it had no effect when injections were given to animals bearing larger tumors. There were no signs of toxicity or unwanted systemic effects. We also observed evidence of increased perfusion, vessel number, response to 15 Gy radiation and oxygenation in RERF tumors of animals injected with BOECs compared to control tumors. In addition, FSaII murine fibrosarcoma tumors were found to grow faster upon injection of BOECs. When FSaII tumors were subjected to a partial thermal ablation treatment using high intensity focused ultrasound (HIFU) there was consistently elevated detection of fluorescently labeled and i.v. injected endothelial precursors in the tumor when analyzed with optical imaging and/or histological preparations. Importantly, we also observed that BOECs treated with the novel anti-angiogenic peptide anginex in-vitro, show decreased proliferation and increased sensitivity to radiation. In vivo, the normal increase in FSaII tumor growth induced by injected BOECs was blunted by the addition of anginex treatment. It appears that endothelial precursors may significantly contribute to tumor vessel growth, tumor progression and/or repair of tumor damage and may improve the

  1. Altered drug binding to serum proteins in pregnant women: therapeutic relevance.

    OpenAIRE

    Perucca, E; Ruprah, M; Richens, A

    1981-01-01

    The binding of diazepam, phenytoin and valproic acid to serum proteins in vitro has been compared in pregnant women of different gestational ages and in controls. The unbound fraction of each of three drugs was elevated during pregnancy (particularly during the last 8 weeks) probably due, at least in part, to a fall in serum albumin concentration. These findings may provide a partial explanation for the increase in the clearance of certain drugs during pregnancy and need to be taken into acco...

  2. Mycobacterium biofilms: factors involved in development, dispersal, and therapeutic strategies against biofilm-relevant pathogens.

    Science.gov (United States)

    Xiang, Xiaohong; Deng, Wanyan; Liu, Minqiang; Xie, Jianping

    2014-01-01

    Many bacteria can develop biofilm (BF), a multicellular structure largely combining bacteria and their extracellular polymeric substances (EPS). The formation of biofilm results in an alternative existence in which microbes ensure their survival in adverse environments. Biofilm-relevant infections are more persistent, resistant to most antibiotics, and more recalcitrant to host immunity. Mycobacterium tuberculosis, the causative agent of tuberculosis, can develop biofilm, though whether M. tuberculosis can form biofilm within tuberculosis patients has yet to be determined. Here, we summarize the factors involved in the development and dispersal of mycobacterial biofilms, as well as underlying regulatory factors and inhibitors against biofilm to deepen our understanding of their development and to elucidate potential novel modes of action for future antibiotics. Key factors in biofilm formation identified as drug targets represent a novel and promising avenue for developing better antibiotics.

  3. Podoplanin emerges as a functionally relevant oral cancer biomarker and therapeutic target.

    Science.gov (United States)

    Retzbach, Edward P; Sheehan, Stephanie A; Nevel, Evan M; Batra, Amber; Phi, Tran; Nguyen, Angels T P; Kato, Yukinari; Baredes, Soly; Fatahzadeh, Mahnaz; Shienbaum, Alan J; Goldberg, Gary S

    2018-03-01

    Oral cancer has become one of the most aggressive types of cancer, killing 140,000 people worldwide every year. Current treatments for oral cancer include surgery and radiation therapies. These procedures can be very effective; however, they can also drastically decrease the quality of life for survivors. New chemotherapeutic treatments are needed to more effectively combat oral cancer. The transmembrane receptor podoplanin (PDPN) has emerged as a functionally relevant oral cancer biomarker and chemotherapeutic target. PDPN expression promotes tumor cell migration leading to oral cancer invasion and metastasis. Here, we describe the role of PDPN in oral squamous cell carcinoma progression, and how it may be exploited to prevent and treat oral cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Nicotine at clinically relevant concentrations affects atrial inward rectifier potassium current sensitive to acetylcholine.

    Science.gov (United States)

    Bébarová, Markéta; Matejovič, Peter; Švecová, Olga; Kula, Roman; Šimurdová, Milena; Šimurda, Jiří

    2017-05-01

    Nicotine abuse is associated with variety of diseases including arrhythmias, most often atrial fibrillation (AF). Altered inward rectifier potassium currents including acetylcholine-sensitive current I K(Ach) are known to be related to AF pathogenesis. Since relevant data are missing, we aimed to investigate I K(Ach) changes at clinically relevant concentrations of nicotine. Experiments were performed by the whole cell patch clamp technique at 23 ± 1 °C on isolated rat atrial myocytes. Nicotine was applied at following concentrations: 4, 40 and 400 nM; ethanol at 20 mM (∼0.09%). Nicotine at 40 and 400 nM significantly activated constitutively active component of I K(Ach) with the maximum effect at 40 nM (an increase by ∼100%); similar effect was observed at -110 and -50 mV. Changes at 4 nM nicotine were negligible on average. Coapplication of 40 nM nicotine and 20 mM ethanol (which is also known to activate this current) did not show cumulative effect. In the case of acetylcholine-induced component of I K(Ach) , a dual effect of nicotine and its correlation with the current magnitude in control were apparent: the current was increased by nicotine in the cells showing small current in control and vice versa. The effect of 40 and 400 nM nicotine on acetylcholine-induced component of I K(Ach) was significantly different at -110 and -50 mV. We conclude that nicotine at clinically relevant concentrations significantly increased constitutively active component of I K(Ach) and showed a dual effect on its acetylcholine-induced component, similarly as ethanol. Synchronous application of nicotine and ethanol did not cause additive effect.

  5. Stunning in radioiodine therapy of benign thyroid disease. Quantification and therapeutic relevance

    International Nuclear Information System (INIS)

    Krohn, T.; Meyer, P.T.; Knollmann, D.; Nowak, B.; Schaefer, W.M.; Ocklenburg, C.

    2008-01-01

    In radioiodine therapy of benign thyroid disease, a reduction of radioiodine uptake is known for consecutive administrations of 131I, which needs to be considered in therapy planning. Aim: Analysis of uptake reduction with regard on the time interval between radioiodine administration and the delivered dose to the thyroid tissue. Patients, methods: 200 patients were enrolled in the study and distributed into two groups (matched for diagnoses), each containing 32 patients with Graves' disease (target dose 250 Gy), 24 with focal (400 Gy), 44 with disseminated thyroid autonomy (150 Gy). In one group, a second fraction of radioiodine was given after 48 h (2d) due to an unexpected low radioiodine uptake or effective half-life, whereas in the other group the second fraction was given after 96 h (4d). Results: There was no significant difference between delivered doses due to the first fraction after four days: 2d: 86 ± 48 Gy (extrapolated) vs. 4d: 87 ± 41 Gy, p > 0.05. In 2d, delivered dose at time of second administration was significantly lower (51 μ 29 Gy) than in 4d (p < 0.01). The radioiodine uptake of the second fraction relative to the initial uptake was significantly lower in the 4d (4d: 63 ± 25% vs. 2d: 82 ± 24%, p < 0.01). In addition, a correlation between uptake reduction and delivered dose and an influence of the time interval between radioiodine administrations could be shown. Conclusions: Relative uptake of subsequent radioiodine fractions decreases with time after first administration and with increasing delivered dose to the thyroid. If a second fraction of 131I is given at an earlier time, the same therapeutic effect can be reached using lower amounts of activity, minimising radiation exposure and increasing efficiency of radioiodine therapy. (orig.)

  6. Therapeutic relevance of the PP2A-B55 inhibitory kinase MASTL/Greatwall in breast cancer.

    Science.gov (United States)

    Álvarez-Fernández, Mónica; Sanz-Flores, María; Sanz-Castillo, Belén; Salazar-Roa, María; Partida, David; Zapatero-Solana, Elisabet; Ali, H Raza; Manchado, Eusebio; Lowe, Scott; VanArsdale, Todd; Shields, David; Caldas, Carlos; Quintela-Fandino, Miguel; Malumbres, Marcos

    2017-12-11

    PP2A is a major tumor suppressor whose inactivation is frequently found in a wide spectrum of human tumors. In particular, deletion or epigenetic silencing of genes encoding the B55 family of PP2A regulatory subunits is a common feature of breast cancer cells. A key player in the regulation of PP2A/B55 phosphatase complexes is the cell cycle kinase MASTL (also known as Greatwall). During cell division, inhibition of PP2A-B55 by MASTL is required to maintain the mitotic state, whereas inactivation of MASTL and PP2A reactivation is required for mitotic exit. Despite its critical role in cell cycle progression in multiple organisms, its relevance as a therapeutic target in human cancer and its dependence of PP2A activity is mostly unknown. Here we show that MASTL overexpression predicts poor survival and shows prognostic value in breast cancer patients. MASTL knockdown or knockout using RNA interference or CRISPR/Cas9 systems impairs proliferation of a subset of breast cancer cells. The proliferative function of MASTL in these tumor cells requires its kinase activity and the presence of PP2A-B55 complexes. By using a new inducible CRISPR/Cas9 system in breast cancer cells, we show that genetic ablation of MASTL displays a significant therapeutic effect in vivo. All together, these data suggest that the PP2A inhibitory kinase MASTL may have both prognostic and therapeutic value in human breast cancer.

  7. [Influence of reverse osmosis concentrate on physicochemical parameters of Sini decoction material system and their relevance].

    Science.gov (United States)

    Jin, Tang-Hui; Zhang, Liu-Hong; Zhu, Hua-Xu; Guo, Li-Wei; Li, Bo; Lu, Ming-Ming

    2014-04-01

    By studying the process of reverse osmosis system for traditional Chinese medicine materials physicochemical parameters affecting the osmotic pressure of its relevance, new compound system reverse osmosis process design methods were explored. Three concentrations materials for high, middle and low were dubbed with Sini decoction as a model drug, and pretreated by 50 thousand relative molecular weight cut-off ultrafiltration membrane. The viscosity, turbidity, conductivity, salinity, TDS, pH value and osmotic pressure of each sample were determined after the reverse osmosis to study the physical and chemical parameters between their respective correlations with the osmotic pressure, and characterized by HPLC chromatograms showing changes before and after the main chemical composition of samples of reverse osmosis. Conductivity-osmotic pressure, salinity-osmotic pressure of the linear correlation coefficient, TDS-osmotic pressure between the three sets of parameters were 0.963 8, 0.932 7, 0.973 7, respectively. Reverse osmosis concentrate and its characteristic spectrum ultrafiltrate HPLC similarity were up to 0. 968 or more, except the low concentrations. There is a significant correlation between the three physicochemical parameters (conductivity, salinity, TDS) and osmotic pressure of each sample system, and there is also significant linear correlation between salinity, conductivity, TDS. The original chemical composition of Sini decoction material concentrate was completely remained after the process of reverse osmosis.

  8. Determination of the relevant market as a criterion of assessment of concentration effects in the practice of antitrust authorities

    Directory of Open Access Journals (Sweden)

    Daria Kostecka-Jurczyk

    2012-12-01

    Full Text Available Determining the relevant market is the first and the most important step in antimonopoly proceedings due to the fact that the market position of an enterprise is always determined from the relevant market perspective. In respect of mergers, establishing the relevant market is essential in analysing whether the aim of the concentration is to distort and limit competition on the market. The author of the article focuses on describing methods for determining the relevant market applied by antimonopoly authorities.

  9. Direct toxic effects of aqueous extract of cigarette smoke on cardiac myocytes at clinically relevant concentrations

    International Nuclear Information System (INIS)

    Yamada, Shigeyuki; Zhang Xiuquan; Kadono, Toshie; Matsuoka, Nobuhiro; Rollins, Douglas; Badger, Troy; Rodesch, Christopher K.; Barry, William H.

    2009-01-01

    Aims: Our goal was to determine if clinically relevant concentrations of aqueous extract of cigarette smoke (CSE) have direct deleterious effects on ventricular myocytes during simulated ischemia, and to investigate the mechanisms involved. Methods: CSE was prepared with a smoking chamber. Ischemia was simulated by metabolic inhibition (MI) with cyanide (CN) and 0 glucose. Adult rabbit and mouse ventricular myocyte [Ca 2+ ] i was measured by flow cytometry using fluo-3. Mitochondrial [Ca 2+ ] was measured with confocal microscopy, and Rhod-2 fluorescence. The mitochondrial permeability transition (MPT) was detected by TMRM fluorescence and myocyte contracture. Myocyte oxidative stress was quantified by dichlorofluorescein (DCF) fluorescence with confocal microscopy. Results: CSE 0.1% increased myocyte contracture caused by MI. The nicotine concentration (HPLC) in 0.1% CSE was 15 ng/ml, similar to that in humans after smoking cigarettes. CSE 0.1% increased mitochondrial Ca 2+ uptake, and increased the susceptibility of mitochondria to the MPT. CSE 0.1% increased DCF fluorescence in isolated myocytes, and increased [Ca 2+ ] i in paced myocytes exposed to 2.0 mM CN, 0 glucose (P-MI). These effects were inhibited by the superoxide scavenger Tiron. The effect of CSE on [Ca 2+ ] i during P-MI was also prevented by ranolazine. Conclusions: CSE in clinically relevant concentrations increases myocyte [Ca 2+ ] i during simulated ischemia, and increases myocyte susceptibility to the MPT. These effects appear to be mediated at least in part by oxidative radicals in CSE, and likely contribute to the effects of cigarette smoke to increase myocardial infarct size, and to decrease angina threshold

  10. Therapeutic effects of various concentrations of lincomycin in drinking water on experimentally transmitted swine dysentery.

    Science.gov (United States)

    Hamdy, A H

    1978-07-01

    Three experimental studies were conducted in 232 growing pigs (8 to 12 weeks old) to evaluate the therapeutic effects of various concentrations of lincomycin in drinking water, against swine dysentery experimentally transmitted, by oral inoculation or by contact-commingling exposure. Four or 5 concentrations of lincomycin were used in each experiment (132, 66, 33, 16.5 or 0.0 mg/L of drinking water). Medication was initiated 7 to days after exposure and was continued for 6 to 10 days. Both methods of exposure were capable of transmitting the disease successfully. A more marked dose response was noticed in pigs inoculated orally than in pigs that were exposed by contact. All concentrations of lincomycin were effective for the treatment of swine dysentery by oral or by contact exposure. At the smaller concentration of 16.5 mg/L of drinking water, lincomycin was less effective for treating the disease than it was at greater concentrations. The suggested optimal concentration was 33 mg of lincomycin/L of drinking water for the treatment of swine dysentery.

  11. [Relation between dose, plasma concentration and therapeutic effect of theophylline in children with sleep apnea].

    Science.gov (United States)

    Rodríguez-Palomares, C; Ugartechea, J C; Palma-Aguirre, J A; Juárez-Olguín, H; Calderón-Mandujano, B

    1989-12-01

    The plasma concentration of theophylline was determined in twelve children with infantile sleep apnea (average age 48.5 days). The purpose of the study was to correlate concentrations with the dosages given, the therapeutic response and any adverse effects which could arise. In addition, other pharmacokinetic values were found, half-life (t 1/2) and clearance concentrations (Clss). The oral maintenance dose used was 4 mg/kg/24 h. The serum concentration of theophylline was determined by a homogeneous immunoassay enzyme technique (EMIT). A bad correlation was found (r = 0.45) between the oral dosage given and the plasma concentrations found. This was probably due to variations in the clearance of the drug. Yet, plasma concentrations fell between 3.0 and 12.6 micrograms/mL, enough to satisfactorily control apneic episodes in all the children included in the study without undesirable side-effects. Only one patient had some trouble in falling asleep and showed signs of irritability. The half-life was 13.30 +/- 7.46 hours and Clss was 36.64 +/- 12.98 mL/h/kg. In general, our results correlate with those reported in the literature. The accuracy of the pharmacokinetic parameters with two samples is reliable, therefore avoiding the use of multiple sampling in this group of children.

  12. How cyclophosphamide at environmentally relevant concentration influences Daphnia magna life history and its proteome.

    Directory of Open Access Journals (Sweden)

    Małgorzata Grzesiuk

    Full Text Available The waste of commonly used medicines is known to contaminate freshwater ecosystems. Pharmaceuticals can be toxic, mutagenic, or modifying to freshwater organisms even at low concentrations if consider their permanent presence in the environment. Chemotherapeutics used to treat cancer, and in particular alkylating agents, contribute significantly to this form of pollution, the latter introducing cytotoxic and/or mutagenic lesions to the DNA and RNA of organisms which can be disruptive to their cells. The aim of the present study was to investigate the influence of the alkylating anticancer agent cyclophosphamide (CP on Daphnia magna clones. We evaluated the life history parameters and protein profiles of this crustacean following exposure to environmentally relevant CP concentration of 10 ng L-1. Even at this low concentration, the alkylating agent caused modification of the life history parameters and proteome profile of the Daphnia. These changes were clone-specific and involved growth rate, age at first reproduction, neonate number, and proteins related to cell cycle and redox state regulation. The disturbance caused by pharmaceuticals contaminating freshwater ecosystem is probably weaker and unlikely to be cytotoxic in character due to the high dilution of these substances in the water. However, our results indicate that prolonged exposure of organisms to these toxins may lead to modifications on the organismal and molecular levels with unpredictable significance for the entire ecosystem.

  13. Bumblebees are not deterred by ecologically relevant concentrations of nectar toxins.

    Science.gov (United States)

    Tiedeken, Erin Jo; Stout, Jane C; Stevenson, Philip C; Wright, Geraldine A

    2014-05-01

    Bees visit flowers to collect nectar and pollen that contain nutrients and simultaneously facilitate plant sexual reproduction. Paradoxically, nectar produced to attract pollinators often contains deterrent or toxic plant compounds associated with herbivore defence. The functional significance of these nectar toxins is not fully understood, but they may have a negative impact on pollinator behaviour and health, and, ultimately, plant pollination. This study investigates whether a generalist bumblebee, Bombus terrestris, can detect naturally occurring concentrations of nectar toxins. Using paired-choice experiments, we identified deterrence thresholds for five compounds found in the nectar of bee-pollinated plants: quinine, caffeine, nicotine, amygdalin and grayanotoxin. The deterrence threshold was determined when bumblebees significantly preferred a sucrose solution over a sucrose solution containing the compound. Bumblebees had the lowest deterrence threshold for the alkaloid quinine (0.01 mmol l(-1)); all other compounds had higher deterrence thresholds, above the natural concentration range in floral nectar. Our data, combined with previous work using honeybees, suggest that generalist bee species have poor acuity for the detection of nectar toxins. The fact that bees do not avoid nectar-relevant concentrations of these compounds likely indicates that it is difficult for them to learn to associate floral traits with the presence of toxins, thus maintaining this trait in plant populations.

  14. Effects of tributyltin on metamorphosis and gonadal differentiation of Xenopus laevis at environmentally relevant concentrations.

    Science.gov (United States)

    Shi, Huahong; Zhu, Pan; Guo, Suzhen

    2014-05-01

    Tributyltin (TBT), a well known endocrine disruptor, has high teratogenicity to embryos of amphibian (Xenopus tropicalis). An amphibian metamorphosis assay (AMA) and a complete AMA (CAMA) were conducted for TBT. In AMA, the body weight, the snout-to-vent length and the hind limb length of X. laevis tadpoles were decreased in tributyltin chloride (TBTCl; 12.5-200 ng/L) treatment groups after 7 days exposure. TBT greatly retarded the development of tadpoles, decreased the number of follicle and induced thyroid follicle cell hyperplasia after 19 days exposure. In CAMA, 10 and 100 ng/L TBTCl led to various malformations of gonad, including intersex, segmental aplasia and multiple ovary cavities of X. laevis following exposure from stages 46 to stage 66. The sex ratio was male-biased in TBT treatment groups. These results suggest that TBT delayed the metamorphosis, inhibited the growth of tadpoles and disrupted the gonadal differentiation of X. laevis at environmentally relevant concentrations.

  15. Effects of tributyltin (TBT) on Xenopus tropicalis embryos at environmentally relevant concentrations.

    Science.gov (United States)

    Guo, Suzhen; Qian, Lijuan; Shi, Huahong; Barry, Terence; Cao, Qinzhen; Liu, Junqi

    2010-04-01

    Tributyltin (TBT) has been widely used as a biocide in antifouling paints and is a known endocrine disrupting chemical. In this paper, we exposed embryos of Xenopus tropicalis to 50-400ngL(-1) tributyltin chloride. TBT significantly decreased the survival rate, reduced the body length and retarded the development of embryos after 24, 36 and 48h of exposure. These effects of TBT were concentration- and time-dependent. Embryos treated with TBT showed multiple malformations. The most obvious alterations were abnormal eyes, enlarged proctodaeum, narrow fins, and skin hypopigmentation. Enlarged proctodaeum and narrow fins were mainly observed after 36 and 48h of exposure. The loss of eye pigmentation or the absence of external eyes occurred after 24 and 36h of exposure, while extended lenses or edemas of eyes were more commonly observed after 48h of exposure. Additional malformations included: small anterior region of heads, pericardial edemas, enlarged trunks, and bent tails. These results suggested that TBT is very toxic to X. tropicalis embryos at environmentally relevant concentrations.

  16. Detection of Adriamycin-DNA adducts by accelerator mass spectrometry at clinically relevant Adriamycin concentrations.

    Science.gov (United States)

    Coldwell, Kate E; Cutts, Suzanne M; Ognibene, Ted J; Henderson, Paul T; Phillips, Don R

    2008-09-01

    Limited sensitivity of existing assays has prevented investigation of whether Adriamycin-DNA adducts are involved in the anti-tumour potential of Adriamycin. Previous detection has achieved a sensitivity of a few Adriamycin-DNA adducts/10(4) bp DNA, but has required the use of supra-clinical drug concentrations. This work sought to measure Adriamycin-DNA adducts at sub-micromolar doses using accelerator mass spectrometry (AMS), a technique with origins in geochemistry for radiocarbon dating. We have used conditions previously validated (by less sensitive decay counting) to extract [(14)C]Adriamycin-DNA adducts from cells and adapted the methodology to AMS detection. Here we show the first direct evidence of Adriamycin-DNA adducts at clinically-relevant Adriamycin concentrations. [(14)C]Adriamycin treatment (25 nM) resulted in 4.4 +/- 1.0 adducts/10(7) bp ( approximately 1300 adducts/cell) in MCF-7 breast cancer cells, representing the best sensitivity and precision reported to date for the covalent binding of Adriamycin to DNA. The exceedingly sensitive nature of AMS has enabled over three orders of magnitude increased sensitivity of Adriamycin-DNA adduct detection and revealed adduct formation within an hour of drug treatment. This method has been shown to be highly reproducible for the measurement of Adriamycin-DNA adducts in tumour cells in culture and can now be applied to the detection of these adducts in human tissues.

  17. Effect of ethanol at clinically relevant concentrations on atrial inward rectifier potassium current sensitive to acetylcholine.

    Science.gov (United States)

    Bébarová, Markéta; Matejovič, Peter; Pásek, Michal; Hořáková, Zuzana; Hošek, Jan; Šimurdová, Milena; Šimurda, Jiří

    2016-10-01

    Alcohol intoxication tends to induce arrhythmias, most often the atrial fibrillation. To elucidate arrhythmogenic mechanisms related to alcohol consumption, the effect of ethanol on main components of the ionic membrane current is investigated step by step. Considering limited knowledge, we aimed to examine the effect of clinically relevant concentrations of ethanol (0.8-80 mM) on acetylcholine-sensitive inward rectifier potassium current I K(Ach). Experiments were performed by the whole-cell patch clamp technique at 23 ± 1 °C on isolated rat and guinea-pig atrial myocytes, and on expressed human Kir3.1/3.4 channels. Ethanol induced changes of I K(Ach) in the whole range of concentrations applied; the effect was not voltage dependent. The constitutively active component of I K(Ach) was significantly increased by ethanol with the maximum effect (an increase by ∼100 %) between 8 and 20 mM. The changes were comparable in rat and guinea-pig atrial myocytes and also in expressed human Kir3.1/3.4 channels (i.e., structural correlate of I K(Ach)). In the case of the acetylcholine-induced component of I K(Ach), a dual ethanol effect was apparent with a striking heterogeneity of changes in individual cells. The effect correlated with the current magnitude in control: the current was increased by eth-anol in the cells showing small current in control and vice versa. The average effect peaked at 20 mM ethanol (an increase of the current by ∼20 %). Observed changes of action potential duration agreed well with the voltage clamp data. Ethanol significantly affected both components of I K(Ach) even in concentrations corresponding to light alcohol consumption.

  18. Early stress responses in Atlantic salmon (Salmo salar) exposed to environmentally relevant concentrations of uranium

    International Nuclear Information System (INIS)

    Song You; Salbu, Brit; Heier, Lene Sørlie; Teien, Hans-Christian; Lind, Ole-Christian; Oughton, Deborah; Petersen, Karina; Rosseland, Bjørn Olav; Skipperud, Lindis; Tollefsen, Knut Erik

    2012-01-01

    Uranium (U) is a naturally occurring heavy metal widely used in many military and civil applications. Uranium contamination and the associated potential adverse effects of U on the aquatic environment have been debated during recent years. In order to understand the effect and mode of action (MoA) of U in vivo, juvenile Atlantic salmon (Salmo salar) were exposed to 0.25 mg/L, 0.5 mg/L and 1.0 mg/L waterborne depleted uranyl acetate, respectively, in a static system for 48 h. The U concentrations in the gill and liver were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) and the resulting biological effects were determined by a combination of analysis of gene expression and micronuclei formation. The hepatic transcriptional level of 12 biomarker genes from four stress–response categories, including oxidative stress (γ-glutamyl cysteine synthetase (GCS), glutathione reductase (GR), glutathione peroxidase (GPx)), DNA damage and repair (P53, cyclin-dependent kinase inhibitor 1 (P21), growth arrest and DNA damage-inducible gene gamma (Gadd45G), proliferating cell nuclear antigen (PCNA), Rad51), apoptosis (Bcl2-associated X protein (BAX), Bcl-x, Caspase 6A,) and protein degradation (Ubiquitin) were evaluated by quantitative real-time polymerase chain reaction (q-rtPCR). The results clearly showed accumulation of U in the gill and liver with increasing concentrations of U in the exposure water. The effects of U on differential hepatic gene expression also occurred in a concentration-dependent manner, although deviations from ideal concentration–response relationships were observed at the highest U concentration (1.0 mg/L). All the genes tested were found to be up-regulated by U while no significant micronuclei formation was identified. The results suggest that U may cause oxidative stress in fish liver at concentrations greater than 0.25 mg/L, giving rise to clear induction of several toxicologically relevant biomarker genes, although no significant

  19. Therapeutic serum phenobarbital concentrations obtained using chronic transdermal administration of phenobarbital in healthy cats.

    Science.gov (United States)

    Delamaide Gasper, Joy A; Barnes Heller, Heidi L; Robertson, Michelle; Trepanier, Lauren A

    2015-04-01

    Seizures are a common cause of neurologic disease, and phenobarbital (PB) is the most commonly used antiepileptic drug. Chronic oral dosing can be challenging for cat owners, leading to poor compliance. The purpose of this study was to determine if the transdermal administration of PB could achieve serum PB concentrations of between 15 and 45 μg/ml in healthy cats. Nineteen healthy cats were enrolled in three groups. Transdermal PB in pluronic lecithin organogel (PLO) was applied to the pinnae for 14 days at a dosage of 3 mg/kg q12h in group 1 (n = 6 cats) and 9 mg/kg q12h in group 2 (n = 7 cats). Transdermal PB in Lipoderm Activemax was similarly applied at 9 mg/kg q12h for 14 days in group 3 (n = 6 cats). Steady-state serum PB concentrations were measured at trough, and at 2, 4 and 6 h after the morning dose on day 15. In group 1, median concentrations ranged from 6.0-7.5 μg/ml throughout the day (observed range 0-11 μg/ml). Group 2 median concentrations were 26.0 μg/ml (observed range 18.0-37.0 μg/ml). For group 3, median concentrations ranged from 15.0-17.0 μg/ml throughout the day (range 5-29 μg/ml). Side effects were mild. One cat was withdrawn from group 2 owing to ataxia and sedation. These results show therapeutic serum PB concentrations can be achieved in cats following chronic transdermal administration of PB in PLO at a dosage of 9 mg/kg q12h. More individual variation was noted using Lipoderm Activemax. Transdermal administration may be an alternative for cats that are difficult to medicate orally. © ISFM and AAFP 2014.

  20. Effects of therapeutic plasma exchange on serum immunoglobulin concentrations in a dog with refractory immune-mediated hemolytic anemia.

    Science.gov (United States)

    Scagnelli, Alyssa M; Walton, Stuart A; Liu, Chin-Chi; Acierno, Mark J

    2018-05-01

    CASE DESCRIPTION A 9-year-old 8.3-kg (18.3-lb) neutered male Miniature Schnauzer was referred for diagnosis and treatment of a sudden onset of lethargy, anorexia, vomiting, and pallor. CLINICAL FINDINGS On physical examination, the dog was lethargic with pale mucous membranes and a capillary refill time ≥ 2 seconds. Skin and sclera were mildly icteric. Signs of pain were elicited during abdominal palpation, and an enlarged spleen was noted. Results of agglutination testing and cytologic findings were consistent with immune-mediated hemolytic anemia (IMHA). No contributing factors for development of IMHA were identified. TREATMENT AND OUTCOME Initial treatment included management with immunosuppressant medications. Three packed RBC transfusions were administered, but clinical signs continued to progress. Therefore, therapeutic plasma exchange (TPE) was performed 5 and 9 days after admission. Following each TPE procedure, the dog had an appreciable clinical improvement and decrease in RBC autoagglutination, and the Hct stabilized. Serum IgG and IgM concentrations were measured during and after both TPE procedures. Despite anticoagulative treatment, the dog developed a thrombus in the splenic vein, necessitating a splenectomy. CLINICAL RELEVANCE The decrease and rebound in serum IgG and IgM concentrations following TPE provided evidence that TPE may have the same immunomodulatory effects in dogs as have been proposed to occur in people. Further, findings suggested that TPE may be a useful alternative in dogs with refractory IMHA when traditional treatments fail.

  1. Therapeutic efficacy and safety evaluation of erythrocyte concentrate used in dogs

    Directory of Open Access Journals (Sweden)

    Ildiko Barabasi

    2016-11-01

    Full Text Available Therapeutic efficacy and safety evaluation of erythrocyte concentrate used in dogs 1Ildikó BARABÁSI, 1Cristina ȘTEFǍNUȚ, 1Laurenţ OGNEAN 1University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, 400037, Manastur street, no.3-5, Cluj-Napoca, Romania *Corresponding author: lognean@yahoo.com   Keywords: dogs, erythrocyte concentrate, hematocrit, immune-mediated hemolytic anemia, transfusion therapy Introduction: The minimum dose of whole blood products as well as erythrocyte concentrate has been under a lot of debate, new equations for calculating the optimal dose being made up from a large variety of hematologists (Kisielewicz et al 2014; Helm and Knottenbelt, 2010; Gibson, 2007. Aim: The therapeutical efficacy of erythrocyte concentrates in dogs with different types of anemia by measuring the hematocrit level 6 hours after the transfusion and a complete blood count 5 days post-transfusion therapy. Materials and methods: Blood tests were performed with ADIVA hematological analyzer; the 6 hour post-transfusion hematocrit was determined by a micro hematocrit. On admission every patient received a routine blood test that included 40 hematological parameters and 21 biochemical parameters. In addition, a detailed examination of the blood smears was also performed by the ADIVA hematological analyzer with 26 parameters that mostly referred to red blood cell and white blood cell morphology. Blood typing was done using the RapidVet quick test kit. Patients received only type specific blood and to limit transfusion reaction occurrences, in addition, a crossmatch test was performed before every transfusion. Statistical analysis was accomplished with GraphPadInStat 3.0 and the graphical depiction of the obtained results was made using the Origin 8.5. graphics program. Results: Statistical analysis reveal that the total red blood cell count underwent very significant changes (p=0.0052 as well as the hemoglobin (p=0.0085. The hematocrit

  2. Relevance of various animal models of human infections to establish therapeutic equivalence of a generic product of piperacillin/tazobactam.

    Science.gov (United States)

    Agudelo, Maria; Rodriguez, Carlos A; Zuluaga, Andres F; Vesga, Omar

    2015-02-01

    After demonstrating with diverse intravenous antibacterials that pharmaceutical equivalence (PE) does not predict therapeutic equivalence, we tested a single generic product of piperacillin/tazobactam (TZP) in terms of PE, pharmacokinetics and in vitro/vivo pharmacodynamics against several pathogens in neutropenic mouse thigh, lung and brain infection models. A generic product was compared head-to-head against the innovator. PE was evaluated by microbiological assay. Single-dose serum pharmacokinetics were determined in infected mice, and the MIC/MBC were determined by broth microdilution. In vivo experiments were done in a blind fashion. Reproducibility was tested on different days using different infecting organisms and animal models. Neutropenic MPF mice were infected in the thighs with Staphylococcus aureus GRP-0057 or Pseudomonas aeruginosa PA01 and in the lungs or brain with Klebsiella pneumoniae ATCC 10031. Treatment started 2h (thigh and brain) or 14 h (lung) after infection and was administered every 3h over 24h (thigh and lung) or 48 h (brain). Both products exhibited the same MIC/MBC against each strain, yielded overlaid curves in the microbiological assay (P>0.21) and were bioequivalent (IC90 83-117% for AUC test/reference ratio). In vivo, the generic product and innovator were again undistinguishable in all models and against the different bacterial pathogens involved. The relevance of these neutropenic murine models of infection was established by demonstrating their accuracy to predict the biological response following simultaneous treatment with a generic product or the innovator of TZP. Therapeutic equivalence of the generic product was proved in every model and against different pathogens. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  3. Initial diagnosis of therapeutically relevant thoracic lesions in polytraumatised patients; Zur Akutdiagnostik therapierelevanter Thoraxverletzungen bei schwer- und polytraumatisierten Patienten

    Energy Technology Data Exchange (ETDEWEB)

    Danz, B. [Radiologische Abt., Bundeswehrkrankenhaus Ulm (Germany); Biehl, C. [Radiologische Abt., Bundeswehrkrankenhaus Ulm (Germany); Baehren, W. [Radiologische Abt., Bundeswehrkrankenhaus Ulm (Germany)

    1996-04-01

    To determine the value of supine chest radiography in comparison to orientating chest CT in the initial diagnostic evaluation of severely polytraumatised patients. 303 patients with primary indication for a cranial CT following trauma were investigated between 1988 and 1993. After performing the cranial CT all patients underwent a chest CT with an average of 6 CT slices without changing the position of the patient and with a median scan time of 4 minutes. The results of the chest CT were correlated with the findings of the supine chest radiography in regard to therapeutically relevant pathological changes. The sensitivity in detection of pneumothorax in supine chest radiography was 53% versus 97% in CT, atelectasis 20% versus 94%, lung contusion 79% versus 99%, haemotothorax 62% versus 97%. More fractures were found conventionally (sensitivity 94%) than by chest CT (sensitivity 44%). Supine chest radiography of polytraumatised patients is clearly inferior to orientating chest CT in demonstrating posttraumatic lesions; obtaining therapeutically relevant information justifies the additionally needed small amount of time. (orig.) [Deutsch] Das Ziel dieser retrospektiven Untersuchung bestand darin, die Wertigkeit der a.p. Thoraxaufnahme im Liegen im Vergleich zur orientierenden Computertomographie der Thoraxorgane im Rahmen der Akutdiagnostik bei schwer- und polytraumatisierten Patienten zu analysieren. Im Zeitraum von 1988 bis 1993 bestand bei 303 Patienten wegen eines Schaedel-Hirn-Traumas die primaere Indikation zu einem CCT. Im Anschluss an das CCT wurde routinemaessig ein orientierendes CT der Thoraxorgane mit im Durchschnitt 6 Schichten ohne Umlagerung und einem medianen Zeitaufwand von 4 Minuten durchgefuehrt. Die Befunde des CT des Thorax wurden mit den Ergebnissen der durchgefuehrten a.p. Thoraxliegendaufnahmen im Hinblick auf die Erfassung therapierelevanter pathologischer Veraenderungen verglichen. Die Sensitivitaet fuer die Erkennung eines Pneumothorax in

  4. Environmentally relevant concentrations of citalopram partially inhibit feeding in the three-spine stickleback (Gasterosteus aculeatus).

    Science.gov (United States)

    Kellner, M; Porseryd, T; Porsch-Hällström, I; Hansen, S H; Olsén, K H

    2015-01-01

    Selective Serotonin Re-uptake Inhibitors (SSRI) are mood-altering, psychotropic drugs commonly used in the treatment of depression and other psychological illnesses. Many of them are poorly degraded in sewage treatment plants and enter the environment unaltered. In laboratory studies, they have been demonstrated to affect a wide range of behaviours in aquatic organisms. In this study we investigated the effect of a three-week exposure to 0.15 and 1.5 μg/l of the SSRI citalopram dissolved in the ambient water on the feeding behaviour in three-spine stickleback (Gasterosteus aculeatus). Feeding, measured as the number of attacks performed on a piece of frozen bloodworms during a 10-min period, was reduced by 30-40% in fish exposed to both 0.15 and 1.5 μg/l citalopram. The effects of the environmentally relevant concentration 0.15 μg/l on feeding, an important fitness characteristic, suggests that the ecological significance of environmental SSRI exposure may be pronounced. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Ketoconazole inhibits the cellular uptake of anandamide via inhibition of FAAH at pharmacologically relevant concentrations.

    Directory of Open Access Journals (Sweden)

    Emmelie Björklund

    Full Text Available The antifungal compound ketoconazole has, in addition to its ability to interfere with fungal ergosterol synthesis, effects upon other enzymes including human CYP3A4, CYP17, lipoxygenase and thromboxane synthetase. In the present study, we have investigated whether ketoconazole affects the cellular uptake and hydrolysis of the endogenous cannabinoid receptor ligand anandamide (AEA.The effects of ketoconazole upon endocannabinoid uptake were investigated using HepG2, CaCo2, PC-3 and C6 cell lines. Fatty acid amide hydrolase (FAAH activity was measured in HepG2 cell lysates and in intact C6 cells. Ketoconazole inhibited the uptake of AEA by HepG2 cells and CaCo2 cells with IC50 values of 17 and 18 µM, respectively. In contrast, it had modest effects upon AEA uptake in PC-3 cells, which have a low expression of FAAH. In cell-free HepG2 lysates, ketoconazole inhibited FAAH activity with an IC50 value (for the inhibitable component of 34 µM.The present study indicates that ketoconazole can inhibit the cellular uptake of AEA at pharmacologically relevant concentrations, primarily due to its effects upon FAAH. Ketoconazole may be useful as a template for the design of dual-action FAAH/CYP17 inhibitors as a novel strategy for the treatment of prostate cancer.

  6. Altered pairing behaviour and reproductive success in white ibises exposed to environmentally relevant concentrations of methylmercury.

    Science.gov (United States)

    Frederick, Peter; Jayasena, Nilmini

    2011-06-22

    Methylmercury (MeHg) is the most biologically available and toxic form of mercury, and can act as a powerful teratogen, neurotoxin and endocrine disruptor in vertebrates. However, mechanisms of endocrine impairment and net effects on demography of biota are poorly understood. Here, we report that experimental exposure of an aquatic bird over 3 years to environmentally relevant dietary MeHg concentrations (0.05-0.3 ppm wet weight) resulted in dose-related increases in male-male pairing behaviour (to 55% of males), and decreases in egg productivity (to 30%). Dosed males showed decreased rates of key courtship behaviours, and were approached less by courting females in comparison to control males. Within dosed groups, homosexual males showed a similar reduction when compared with dosed heterosexual males. We found an average 35 per cent decrease in fledgling production in high-dose birds over the study duration. These results are of interest because (i) MeHg exposure is experimentally tied to demographically important reproductive deficits, (ii) these effects were found at low, chronic exposure levels commonly experienced by wildlife, and (iii) effects on reproductive behaviour and sexual preference mediated by endocrine disruption represent a novel and probably under-reported mechanism by which contaminants may influence wild populations of birds.

  7. Api m 10, a genuine A. mellifera venom allergen, is clinically relevant but underrepresented in therapeutic extracts.

    Science.gov (United States)

    Blank, S; Seismann, H; Michel, Y; McIntyre, M; Cifuentes, L; Braren, I; Grunwald, T; Darsow, U; Ring, J; Bredehorst, R; Ollert, M; Spillner, E

    2011-10-01

    Generalized systemic reactions to stinging hymenoptera venom constitute a potentially fatal condition in venom-allergic individuals. Hence, the identification and characterization of all allergens is imperative for improvement of diagnosis and design of effective immunotherapeutic approaches. Our aim was the immunochemical characterization of the carbohydrate-rich protein Api m 10, an Apis mellifera venom component and putative allergen, with focus on the relevance of glycosylation. Furthermore, the presence of Api m 10 in honeybee venom (HBV) and licensed venom immunotherapy preparations was addressed. Api m 10 was produced as soluble, aglycosylated protein in Escherichia coli and as differentially glycosylated protein providing a varying degree of fucosylation in insect cells. IgE reactivity and basophil activation of allergic patients were analyzed. For detection of Api m 10 in different venom preparations, a monoclonal human IgE antibody was generated. Both, the aglycosylated and the glycosylated variant of Api m 10 devoid of cross-reactive carbohydrate determinants (CCD), exhibited IgE reactivity with approximately 50% of HBV-sensitized patients. A corresponding reactivity could be documented for the activation of basophils. Although the detection of the native protein in crude HBV suggested content comparable to other relevant allergens, three therapeutical HBV extracts lacked detectable amounts of this component. Api m 10 is a genuine allergen of A. mellifera venom with IgE sensitizing potential in a significant fraction of allergic patients independent of CCD reactivity. Thus, Api m 10 could become a key element for component-resolved diagnostic tests and improved immunotherapeutic approaches in hymenoptera venom allergy. © 2011 John Wiley & Sons A/S.

  8. Pharmacokinetics and concentration-effect relationships of therapeutic monoclonal antibodies and fusion proteins.

    Science.gov (United States)

    Ternant, David; Paintaud, Gilles

    2005-09-01

    Although monoclonal antibodies (mAbs) constitute a major advance in therapeutics, their pharmacokinetic (PK) and pharmacodynamic (PD) properties are not fully understood. Saturable mechanisms are thought to occur in distribution and elimination of mAbs, which are protected from degradation by the Brambell's receptor (FcRn). The binding of mAbs to their target antigen explains part of their nonlinear PK and PD properties. The interindividual variability in mAb PK can be explained by several factors, including immune response against the biodrug and differences in the number of antigenic sites. The concentration-effect relationships of mAbs are complex and dependent on their mechanism of action. Interindividual differences in mAb PD can be explained by factors such as genetics and clinical status. PK and concentration-effect studies are necessary to design optimal dosing regimens. Because of their above-mentioned characteristics, the interindividual variability in their dose-response relationships must be studied by PK-PD modelling.

  9. Biological effects of environmentally relevant concentrations of the pharmaceutical Triclosan in the marine mussel Perna perna (Linnaeus, 1758)

    Energy Technology Data Exchange (ETDEWEB)

    Sanzi Cortez, Fernando, E-mail: lecotox@unisanta.br [Instituto de Pesquisas Energeticas e Nucleares IPEN-CNEN/SP, 05508-000 Sao Paulo, SP (Brazil); Laboratorio de Ecotoxicologia, Universidade Santa Cecilia, 11045-907 Santos, SP (Brazil); Dias Seabra Pereira, Camilo [Laboratorio de Ecotoxicologia, Universidade Santa Cecilia, 11045-907 Santos, SP (Brazil); Instituto do Mar, Universidade Federal de Sao Paulo, 11030-400 Santos, SP (Brazil); Ramos Santos, Aldo Ramos [Laboratorio de Ecotoxicologia, Universidade Santa Cecilia, 11045-907 Santos, SP (Brazil); Cesar, Augusto; Choueri, Rodrigo Brasil [Laboratorio de Ecotoxicologia, Universidade Santa Cecilia, 11045-907 Santos, SP (Brazil); Instituto do Mar, Universidade Federal de Sao Paulo, 11030-400 Santos, SP (Brazil); Martini, Gisela de Assis [Laboratorio de Ecotoxicologia, Universidade Santa Cecilia, 11045-907 Santos, SP (Brazil); Bohrer-Morel, Maria Beatriz [Instituto de Pesquisas Energeticas e Nucleares IPEN-CNEN/SP, 05508-000 Sao Paulo, SP (Brazil)

    2012-09-15

    Triclosan (5-Chloro-2-(2,4-dichlorophenoxy) phenol) is an antibacterial compound widely employed in pharmaceuticals and personal care products. Although this emerging compound has been detected in aquatic environments, scarce information is found on the effects of Triclosan to marine organisms. The aim of this study was to evaluate the toxicity of a concentration range of Triclosan through fertilization assay (reproductive success), embryo-larval development assay (early life stage) and physiological stress (Neutral Red Retention Time assay - NRRT) (adult stage) in the marine sentinel organism Perna perna. The mean inhibition concentrations for fertilization (IC{sub 50} = 0.490 mg L{sup -1}) and embryo-larval development (IC{sub 50} = 0.135 mg L{sup -1}) tests were above environmental relevant concentrations (ng L{sup -1}) given by previous studies. Differently, significant reduction on NRRT results was found at 12 ng L{sup -1}, demonstrating the current risk of the continuous introduction of Triclosan into aquatic environments, and the need of ecotoxicological studies oriented by the mechanism of action of the compound. - Highlights: Black-Right-Pointing-Pointer Triclosan causes biological adverse effects at environmental relevant concentrations. Black-Right-Pointing-Pointer Mechanisms of action oriented assays were more sensitive to detect biological damages. Black-Right-Pointing-Pointer Currently there is environmental risks concerned Triclosan in aquatic ecosystems. - Triclosan causes biological adverse effects at environmentally relevant concentrations.

  10. Biological effects of environmentally relevant concentrations of the pharmaceutical Triclosan in the marine mussel Perna perna (Linnaeus, 1758)

    International Nuclear Information System (INIS)

    Sanzi Cortez, Fernando; Dias Seabra Pereira, Camilo; Ramos Santos, Aldo Ramos; Cesar, Augusto; Choueri, Rodrigo Brasil; Martini, Gisela de Assis; Bohrer-Morel, Maria Beatriz

    2012-01-01

    Triclosan (5-Chloro-2-(2,4-dichlorophenoxy) phenol) is an antibacterial compound widely employed in pharmaceuticals and personal care products. Although this emerging compound has been detected in aquatic environments, scarce information is found on the effects of Triclosan to marine organisms. The aim of this study was to evaluate the toxicity of a concentration range of Triclosan through fertilization assay (reproductive success), embryo-larval development assay (early life stage) and physiological stress (Neutral Red Retention Time assay - NRRT) (adult stage) in the marine sentinel organism Perna perna. The mean inhibition concentrations for fertilization (IC 50 = 0.490 mg L −1 ) and embryo-larval development (IC 50 = 0.135 mg L −1 ) tests were above environmental relevant concentrations (ng L −1 ) given by previous studies. Differently, significant reduction on NRRT results was found at 12 ng L −1 , demonstrating the current risk of the continuous introduction of Triclosan into aquatic environments, and the need of ecotoxicological studies oriented by the mechanism of action of the compound. - Highlights: ► Triclosan causes biological adverse effects at environmental relevant concentrations. ► Mechanisms of action oriented assays were more sensitive to detect biological damages. ► Currently there is environmental risks concerned Triclosan in aquatic ecosystems. - Triclosan causes biological adverse effects at environmentally relevant concentrations.

  11. Usefulness of estimation of blood procalcitonin concentration versus C-reactive protein concentration and white blood cell count for therapeutic monitoring of sepsis in neonates

    Directory of Open Access Journals (Sweden)

    Agnieszka Kordek

    2014-12-01

    Full Text Available Aim: This study was intended to assess the clinical usefulness of blood procalcitonin (PCT concentrations for the diagnosis and therapeutic monitoring of nosocomial neonatal sepsis.Material/Methods: The enrolment criterion was sepsis clinically manifesting after three days of life. PCT concentrations were measured in venous blood from 52 infected and 88 uninfected neonates. The results were interpreted against C-reactive protein (CRP concentrations and white blood cell counts (WBC.Results: Differences between the two groups in PCT and CRP concentrations were highly significant. No significant differences between the groups were noted for WBC. The threshold value on the receiver operator characteristic curve was 2.06 ng/mL for PCT (SE 75%; SP 80.68%; PPV 62.22%; NPV 88.75%; AUC 0.805, 5.0 mg/L for CRP (SE 67.44%; SP 73.68%; PPV 42.02%; NPV 88.89%; AUC 0.801, and 11.9 x109/L for WBC (SE 51.16%; SP 50.68%; PPV 23.16%; NPV 78.13%; AUC 0.484. Procalcitonin concentrations decreased 24 hours after initiation of antibiotic therapy and reverted to the control level after 5-7 days. C-reactive protein concentrations began to decline after two days of antibiotic therapy but were still higher than in the control group after 5-7 days of treatment. No significant changes in WBC during the treatment were observed.Conclusions: Procalcitonin concentrations in blood appear to be of use for the diagnosis and therapeutic monitoring of nosocomial infections in neonates as this parameter demonstrates greater sensitivity and specificity than C-reactive protein. White blood cell counts appear to be of little diagnostic value in the early phase of infection or for therapeutic monitoring.

  12. Relevance of air conditioning for 222Radon concentration in shops of the Savona Province, Italy

    International Nuclear Information System (INIS)

    Panatto, Donatella; Ferrari, Paola; Lai, Piero; Gallelli, Giovanni

    2006-01-01

    Radon ( 222 Rn) concentration was evaluated in shops of the Savona Province, Italy, between summer 2002 and winter 2002-2003. The main characteristics of each shops were recorded through a questionnaire investigating the ventilation rate and factors related to 222 Rn precursors in the soil and the construction materials. The main variables that were related to radon concentration were the following: age of the building, level of the shop above ground, season of the year, wind exposure, active windows, and type of heating system. Shops equipped with individual air heating/conditioning systems exhibited radon concentrations that were three times higher than those of shops heated by centralized furnaces. Our data indicate that the level of pollution in the shops was of medium level, with an expected low impact on the salespersons' health. Only in wintertime, the action level of 200 Bq m -3 for the confined environment was reached in 10 shops equipped with individual air heating/conditioning systems

  13. Absorption kinetics and steady-state plasma concentrations of theophylline following therapeutic doses of two sustained-release preparations

    DEFF Research Database (Denmark)

    Andersen, O; Nielsen, M K; Eriksen, P B

    1983-01-01

    Ten healthy volunteers received two sustained-release preparations as a single and multiple dose regimen in an open crossover study. Plasma theophylline concentrations were measured by an enzyme immunoassay. The limited fluctuation of the theophylline levels at steady state, with twice daily...... formulation, whereas this was not the case for the other (r = 0.27 and 0.49). The daily dose necessary to keep the plasma concentration within the therapeutic range of 55-110 mumole/liter varied from 7.9 to 22.9 mg/kg. Only mild side effects were recorded, but they were not correlated to the plasma...... theophylline concentration....

  14. EXPOSURE TO ENVIRONMENTALLY RELEVANT CONCENTRATIONS OF DIFFERENT NONYLPHENOL FORMULATIONS IN JAPANESE MEDAKA

    Science.gov (United States)

    The time course of exposure to p-nonylphenol (NP) from two different sources was compared to equivalent exposures of 17-b-estradiol (E2) and a solvent control (ethanol: EtOH). Japanese medaka were exposed for 4 days to a nominal concentration of 20 ?g/l of either NP-I (Schenectad...

  15. Estradiol and endocrine disrupting compounds adversely affect development of sea urchin embryos at environmentally relevant concentrations

    International Nuclear Information System (INIS)

    Roepke, Troy A.; Snyder, Mark J.; Cherr, Gary N.

    2005-01-01

    Environmental endocrine disrupting compounds (EDCs) are a wide variety of chemicals that typically exert effects, either directly or indirectly, through receptor-mediated processes, thus mimicking endogenous hormones and/or inhibiting normal hormone activities and metabolism. Little is known about the effects of EDCs on echinoderm physiology, reproduction and development. We exposed developing sea urchin embryos (Strongylocentrotus purpuratus and Lytechinus anamesus) to two known EDCs (4-octylphenol (OCT), bisphenol A (BisA)) and to natural and synthetic reproductive hormones (17β-estradiol (E 2 ), estrone (E 1 ), estriol (E 3 ), progesterone (P 4 ) and 17α-ethynylestradiol (EE 2 )). In addition, we studied two non-estrogenic EDCs, tributyltin (TBT) and o,p-DDD. Successful development to the pluteus larval stage (96 h post-fertilization) was used to define EDC concentration-response relationships. The order of compound potency based on EC 50 values for a reduction in normal development was as follows: TBT L.anamesus > OCT > TBT S. p urpuratus >> E 2 > EE 2 > DDD >> BisA > P 4 > E 1 >> E 3 . The effect of TBT was pronounced even at concentrations substantially lower than those commonly reported in heavily contaminated areas, but the response was significantly different in the two model species. Sea urchin embryos were generally more sensitive to estrogenic EDCs and TBT than most other invertebrate larvae. Stage-specific exposure experiments were conducted to determine the most sensitive developmental periods using blastula, gastrula and post-gastrula (pluteus) stages. The stage most sensitive to E 2 , OCT and TBT was the blastula stage with less overall sensitivity in the gastrula stage, regardless of concentration. Selective estrogen receptor modulators (SERMs) were added to the experiments individually and in combination with estrogenic EDCs to interfere with potential receptor-mediated actions. Tamoxifen, a partial ER agonist, alone inhibited development at

  16. New mescaline concentrations from 14 taxa/cultivars of Echinopsis spp. (Cactaceae) ("San Pedro") and their relevance to shamanic practice.

    Science.gov (United States)

    Ogunbodede, Olabode; McCombs, Douglas; Trout, Keeper; Daley, Paul; Terry, Martin

    2010-09-15

    The aim of the present study is to determine in a procedurally uniform manner the mescaline concentrations in stem tissue of 14 taxa/cultivars of the subgenus Trichocereus of the genus Echinopsis (Cactaceae) and to evaluate the relationship (if any) between mescaline concentration and actual shamanic use of these plants. Columnar cacti of the genus Echinopsis, some of which are used for diagnostic and therapeutic purposes by South American shamans in traditional medicine, were selected for analysis because they were vegetative clones of plants of documented geographic origin and/or because they were known to be used by practitioners of shamanism. Mescaline content of the cortical stem chlorenchyma of each cactus was determined by Soxhlet extraction with methanol, followed by acid-base extraction with water and dichloromethane, and high-pressure liquid chromatography (HPLC). By virtue of the consistent analytical procedures used, comparable alkaloid concentrations were obtained that facilitated the ranking of the various selected species and cultivars of Echinopsis, all of which exhibited positive mescaline contents. The range of mescaline concentrations across the 14 taxa/cultivars spanned two orders of magnitude, from 0.053% to 4.7% by dry weight. The mescaline concentrations reported here largely support the hypothesis that plants with the highest mescaline concentrations - particularly E. pachanoi from Peru - are most associated with documented shamanic use. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  17. Bisphenol A Induces Superfeminization in the Ramshorn Snail (Gastropoda: Prosobranchia) at Environmentally Relevant Concentrations

    Science.gov (United States)

    Oehlmann, Jörg; Schulte-Oehlmann, Ulrike; Bachmann, Jean; Oetken, Matthias; Lutz, Ilka; Kloas, Werner; Ternes, Thomas A.

    2006-01-01

    Previous investigations have shown that bisphenol A (BPA) induces a superfeminization syndrome in the freshwater snail Marisa cornuarietis at concentrations as low as 1 μg/L. Superfemales are characterized by the formation of additional female organs, enlarged accessory sex glands, gross malformations of the pallial oviduct, and a stimulation of egg and clutch production, resulting in increased female mortality. However, these studies were challenged on the basis of incomplete experimentation. Therefore, the objective of the current approach was to bridge several gaps in knowledge by conducting additional experiments. In an initial series of experiments, study results from the reproductive phase of the snails were evaluated in the sub-micrograms per liter range. Before and after the spawning season, superfemale responses were observed [NOEC (no observed effect concentration) 7.9 ng/L, EC10 (effective concentration at 10%) 13.9 ng/L], which were absent during the spawning season. A further experiment investigated the temperature dependence of BPA responses by exposing snails at two temperatures in parallel. The adverse effect of BPA was at least partially masked at 27°C (EC10 998 ng/L) when compared with 20°C (EC10 14.8 ng/L). In M. cornuarietis, BPA acts as an estrogen receptor (ER) agonist, because effects were completely antagonized by a co-exposure to tamoxifen and Faslodex. Antiandrogenic effects of BPA, such as a significant decrease in penis length at 20°C, were also observed. Competitive receptor displacement experiments indicate the presence of androgen- and estrogen-specific binding sites. The affinity for BPA of the estrogen binding sites in M. cornuarietis is higher than that of the ER in aquatic vertebrates. The results emphasize that prosobranchs are affected by BPA at lower concentrations than are other wildlife groups, and the findings also highlight the importance of exposure conditions. PMID:16818258

  18. Bisphenol A induces superfeminization in the Ramshorn snail Marisa cornuarietis (Gastropoda: Prosobranchia) at environmentally relevant concentrations

    OpenAIRE

    Oehlmann, Jörg; Schulte-Oehlmann, Ulrike; Bachmann, Jean; Oetken, Matthias; Lutz, Ilka; Kloas, Werner; Ternes, Thomas A.

    2007-01-01

    Previous investigations have shown that bisphenol A (BPA) induces a superfeminization syndrome in the freshwater snail Marisa cornuarietis at concentrations as low as 1 μg/L. Superfemales are characterized by the formation of additional female organs, enlarged accessory sex glands, gross malformations of the pallial oviduct, and a stimulation of egg and clutch production, resulting in increased female mortality. However, these studies were challenged on the basis of incomplete experiment...

  19. Transcriptional Response of the Archaeal Ammonia Oxidizer Nitrosopumilus maritimus to Low and Environmentally Relevant Ammonia Concentrations

    OpenAIRE

    Nakagawa, Tatsunori; Stahl, David A.

    2013-01-01

    The ability of chemoautotrophic ammonia-oxidizing archaea to compete for ammonia among marine microorganisms at low ambient concentrations has been in part attributed to their extremely high affinity for ammonia, but as yet there is no mechanistic understanding of supporting metabolism. We examined transcription of selected genes for anabolic functions (CO2 fixation, ammonia transport, and cell wall synthesis) and a central catabolic function (ammonia oxidation) in the thaumarchaeon Nitrosopu...

  20. Estradiol and endocrine disrupting compounds adversely affect development of sea urchin embryos at environmentally relevant concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Roepke, Troy A. [Bodega Marine Laboratory, University of California, Davis, POB 247, Bodega Bay, CA 94923 (United States); Snyder, Mark J. [Bodega Marine Laboratory, University of California, Davis, POB 247, Bodega Bay, CA 94923 (United States); Cherr, Gary N. [Bodega Marine Laboratory, University of California, Davis, POB 247, Bodega Bay, CA 94923 (United States) and Departments of Environmental Toxicology and Nutrition, One Shields Avenue, University of California, Davis, CA 95616 (United States)]. E-mail: gncherr@ucdavis.edu

    2005-01-26

    Environmental endocrine disrupting compounds (EDCs) are a wide variety of chemicals that typically exert effects, either directly or indirectly, through receptor-mediated processes, thus mimicking endogenous hormones and/or inhibiting normal hormone activities and metabolism. Little is known about the effects of EDCs on echinoderm physiology, reproduction and development. We exposed developing sea urchin embryos (Strongylocentrotus purpuratus and Lytechinus anamesus) to two known EDCs (4-octylphenol (OCT), bisphenol A (BisA)) and to natural and synthetic reproductive hormones (17{beta}-estradiol (E{sub 2}), estrone (E{sub 1}), estriol (E{sub 3}), progesterone (P{sub 4}) and 17{alpha}-ethynylestradiol (EE{sub 2})). In addition, we studied two non-estrogenic EDCs, tributyltin (TBT) and o,p-DDD. Successful development to the pluteus larval stage (96 h post-fertilization) was used to define EDC concentration-response relationships. The order of compound potency based on EC{sub 50} values for a reduction in normal development was as follows: TBT {sub L.anamesus} > OCT > TBT {sub S.{sub p}}{sub urpuratus} >> E{sub 2} > EE{sub 2} > DDD >> BisA > P{sub 4} > E{sub 1} >> E{sub 3}. The effect of TBT was pronounced even at concentrations substantially lower than those commonly reported in heavily contaminated areas, but the response was significantly different in the two model species. Sea urchin embryos were generally more sensitive to estrogenic EDCs and TBT than most other invertebrate larvae. Stage-specific exposure experiments were conducted to determine the most sensitive developmental periods using blastula, gastrula and post-gastrula (pluteus) stages. The stage most sensitive to E{sub 2}, OCT and TBT was the blastula stage with less overall sensitivity in the gastrula stage, regardless of concentration. Selective estrogen receptor modulators (SERMs) were added to the experiments individually and in combination with estrogenic EDCs to interfere with potential receptor

  1. Transcriptional Response of the Archaeal Ammonia Oxidizer Nitrosopumilus maritimus to Low and Environmentally Relevant Ammonia Concentrations

    Science.gov (United States)

    Stahl, David A.

    2013-01-01

    The ability of chemoautotrophic ammonia-oxidizing archaea to compete for ammonia among marine microorganisms at low ambient concentrations has been in part attributed to their extremely high affinity for ammonia, but as yet there is no mechanistic understanding of supporting metabolism. We examined transcription of selected genes for anabolic functions (CO2 fixation, ammonia transport, and cell wall synthesis) and a central catabolic function (ammonia oxidation) in the thaumarchaeon Nitrosopumilus maritimus SCM1 growing at two ammonia concentrations, as measured by combined ammonia and ammonium, one well above the Km for ammonia oxidation (∼500 μM) and the other well below the Km (ammonia-replete to ammonia-limiting conditions. Transcript levels for ammonia oxidation, CO2 fixation, and one of the ammonia transport genes were approximately the same at high and low ammonia availability. Transcripts for all analyzed genes decreased with time in the complete absence of ammonia, but with various rates of decay. The new steady-state mRNA levels established are presumably more reflective of the natural physiological state of ammonia-oxidizing archaea and offer a reference for interpreting message abundance patterns in the natural environment. PMID:23995944

  2. Effects of environmentally relevant concentrations of atrazine on gonadal development of snapping turtles (Chelydra serpentina).

    Science.gov (United States)

    de Solla, Shane R; Martin, Pamela A; Fernie, Kimberly J; Park, Brad J; Mayne, Gregory

    2006-02-01

    The herbicide atrazine has been suspected of affecting sexual development by inducing aromatase, resulting in the increased conversion of androgens to estrogens. We used snapping turtles (Chelydra serpentina), a species in which sex is dependent on the production of estrogen through aromatase activity in a temperature-dependent manner, to investigate if environmentally relevant exposures to atrazine affected gonadal development. Eggs were incubated in soil to which atrazine was applied at a typical field application rate (3.1 L/ha), 10-fold this rate (31 L/ha), and a control rate (no atrazine) for the duration of embryonic development. The incubation temperature (25 degrees C) was selected to produce only males. Although some males with testicular oocytes and females were produced in the atrazine-treated groups (3.3-3.7%) but not in the control group, no statistical differences were found among treatments. Furthermore, snapping turtle eggs collected from natural nests in a corn field were incubated at the pivotal temperature (27.5 degrees C) at which both males and females normally would be produced, and some males had oocytes in the testes (15.4%). The presence of low numbers of males with oocytes may be a natural phenomenon, and we have limited evidence to suggest that the presence of normal males with oocytes may represent a feminizing effect of atrazine. Histological examination of the thyroid gland revealed no effect on thyroid morphology.

  3. Radioactive concentrations in foodstuffs and the ingestion dose from Romanian relevant diets

    International Nuclear Information System (INIS)

    Ferdes, O.

    1994-01-01

    Radioactivity measurements of fresh fruits and vegetables, grains (wheat and bread), milk (cheese), meat and meat products from different areas have been done. High-resolution low-level gamma-ray spectrometry, low-level beta total analysis and radiochemical techniques were used. Many radionuclides, both man-made and natural, have been identified. Only a few of them (the man-made Cs, I and Sr as well as the natural 40 K, 7 Be, etc) were of biological importance. In order to predict the ingestion dose, it had to be studied the general pathway of radionuclides to man, including a transfer model to agricultural products and the processes involved in food chain contamination. Modelling the radionuclide behaviour included retention, radioactive decay, metabolic processes and retention after processing. Relevant aspects related to translocation, agricultural practices and food processing were also considered. The human dose due to radioactive intake could be assessed on the basis of a simplified model for radionuclide ingestion and assimilation, considering local conditions and specific diets. As a result the average diets were determined depending on geographical areas (urban, rural, plain and uphill) and age (children, youngsters and adults). The estimated values for yearly ingestion dose vary from a few mSv to tens of mSv (as in the case of 1986 and 1987). (author)

  4. The role of cholesterol metabolism and cholesterol transport in carcinogenesis; A review of scientific findings, relevant to future cancer therapeutics.

    Directory of Open Access Journals (Sweden)

    Pedro Miguel Cruz

    2013-09-01

    Full Text Available While the unique metabolic activities of malignant tissues as potential targets for cancer therapeutics has been the subject of several recent reviews, the role of cholesterol metabolism in this context is yet to be fully explored. Cholesterol is an essential component of mammalian cell membranes as well as a precursor of bile acids and steroid hormones. The hypothesis that cancer cells need excess cholesterol and intermediates of the cholesterol biosynthesis pathway to maintain a high level of proliferation is well accepted, however the mechanisms by which malignant cells and tissues reprogram cholesterol synthesis, uptake and efflux are yet to be fully elucidated as potential therapeutic targets. High and low density plasma lipoproteins, area the likely major suppliers of cholesterol to cancer cells and tumors, potentially via receptor mediated mechanisms. This review is primarily focused on the role(s of lipoproteins in carcinogenesis, and their future roles as drug delivery vehicles for targeted cancer chemotherapy.

  5. Cork stoppers as an effective sorbent for water treatment: the removal of mercury at environmentally relevant concentrations and conditions.

    Science.gov (United States)

    Lopes, Cláudia B; Oliveira, Joana R; Rocha, Luciana S; Tavares, Daniela S; Silva, Carlos M; Silva, Susana P; Hartog, Niels; Duarte, Armando C; Pereira, E

    2014-02-01

    The technical feasibility of using stopper-derived cork as an effective biosorbent towards bivalent mercury at environmentally relevant concentrations and conditions was evaluated in this study. Only 25 mg/L of cork powder was able to achieve 94 % of mercury removal for an initial mercury concentration of 500 μg/L. It was found that under the conditions tested, the efficiency of mercury removal expressed as equilibrium removal percentage does not depend on the amount of cork or its particle size, but is very sensitive to initial metal concentration, with higher removal efficiencies at higher initial concentrations. Ion exchange was identified as one of the mechanisms involved in the sorption of Hg onto cork in the absence of ionic competition. Under ionic competition, stopper-derived cork showed to be extremely effective and selective for mercury in binary mixtures, while in complex matrices like seawater, moderate inhibition of the sorption process was observed, attributed to a change in mercury speciation. The loadings achieved are similar to the majority of literature values found for other biosorbents and for other metals, suggesting that cork stoppers can be recycled as an effective biosorbent for water treatment. However, the most interesting result is that equilibrium data show a very rare behaviour, with the isotherm presenting an almost square convex shape to the concentration axis, with an infinite slope for an Hg concentration in solution around 25 μg/L.

  6. Cytotoxicity of Environmentally Relevant Concentrations of Aluminum in Murine Thymocytes and Lymphocytes

    Directory of Open Access Journals (Sweden)

    Jamal Kamalov

    2011-01-01

    Full Text Available The effects of low concentrations of aluminum chloride on thymocytes and lymphocytes acutely dissociated from young mice were studied using flow cytometry with a DNA-binding dye. We demonstrate a rapid and dose-dependent injury in murine thymocytes and lymphocytes resulting from exposure to aluminum, as indicated by an increase in the entry into the cell of the DNA-binding dye, propidium iodine. A 60-minute exposure to 10 μM AlCl3 caused damage of about 5% of thymocytes, while 50% were injured after 10 minutes at 20 μM. Nearly all thymocytes showed evidence of damage at 30 μM AlCl3 after only 5 minutes of incubation. In lymphocytes, injury was observed at 15 μM AlCl3 and less than 50% of cells were injured after a 60-minute exposure to 20 μM. Injury only rarely proceeded to rapid cell death and was associated with cell swelling. These results suggest that aluminum has cytotoxic effects on cells of the immune system.

  7. Compromising σ-1 receptors at the endoplasmic reticulum render cytotoxicity to physiologically relevant concentrations of dopamine in a nuclear factor-κB/Bcl-2-dependent mechanism: potential relevance to Parkinson's disease.

    Science.gov (United States)

    Mori, Tomohisa; Hayashi, Teruo; Su, Tsung-Ping

    2012-06-01

    The endoplasmic reticulum (ER) chaperone σ-1 receptor (Sig-1R) is cytoprotective against ER stress-induced apoptosis. The level of Sig-1Rs in the brain was reported to be lower in early parkinsonian patients. Because dopamine (DA) toxicity is well known to be involved in the etiology of Parkinson's disease, we tested in this study whether a relationship might exist between Sig-1Rs and DA-induced cytotoxicity in a cellular model by using Chinese hamster ovary (CHO) cells. DA in physiological concentrations (e.g., lower than 10 μM) does not cause apoptosis. However, the same concentrations of DA cause apoptosis in Sig-1R knockdown CHO cells. In search of a mechanistic explanation, we found that unfolded protein response is not involved. Rather, the level of protective protein Bcl-2 is critically involved in this DA/Sig-1R knockdown-induced apoptosis. Specifically, the DA/Sig-1R knockdown causes a synergistic proteasomal conversion of nuclear factor κB (NF-κB) p105 to the active form of p50, which is known to down-regulate the transcription of Bcl-2. It is noteworthy that the DA/Sig-1R knockdown-induced apoptosis is blocked by the overexpression of Bcl-2. Our results therefore indicate that DA is involved in the activation of NF-κB and suggest that endogenous Sig-1Rs are tonically inhibiting the proteasomal conversion/activation of NF-κB caused by physiologically relevant concentrations of DA that would otherwise cause apoptosis. Thus, Sig-1Rs and associated ligands may represent new therapeutic targets for the treatment of parkinsonism.

  8. Loading regimen required to rapidly achieve therapeutic trough plasma concentration of teicoplanin and evaluation of clinical features

    Directory of Open Access Journals (Sweden)

    Seki M

    2012-11-01

    Full Text Available Masafumi Seki,1,* Kaori Yabuno,1,2,* Koji Miyawaki,1,2 Yoshihiro Miwa,2 Kazunori Tomono11Division of Infection Control and Prevention, 2Department of Pharmacy, Osaka University Hospital, Suita, Osaka, Japan*These authors contributed equally to this workBackground: A trough concentration of >20 mg/L is considered the optimal dosage of teicoplanin required to ensure early therapeutic effects against methicillin-resistant Staphylococcus aureus (MRSA infections including those in patients who develop febrile neutropenia after chemotherapy. This study determines appropriate initial doses during the first 2 days of administration and evaluates the therapeutic target teicoplanin trough concentration.Method: A 2-day regimen was evaluated in patients treated with 600 mg and 1200 mg or 1200 mg and 600 mg (total 1800 mg, Group 1, 800 mg and 800 mg (total 1600 mg, Group 2, and 800 mg and 400 mg (total 1200 mg, Group 3 of teicoplanin on Days 1 and 2, respectively. We also compared the efficiency and adverse effects at trough concentrations of 15–20 mg/L (Group A, n = 28 with >20 mg/L (Group B, n = 27 of teicoplanin, and also compared them with those on the similar concentrations of vancomycin (Groups C and D, n = 50 and 34, respectively.Results: The mean trough concentrations of teicoplanin on Days 4 or 5 were 22.2, 17.5, and 16.2 mg/L in Groups 1, 2, and 3, respectively. The clinical efficiency was 85.7%, 81.5%, 92.0%, and 91.5%, in Groups A, B, C, and D, respectively. The rates of adverse effects were not high in teicoplanin (nephrotoxicity, 7.1% and 3.7%, and hepatotoxicity, 14.3% and 11.1% in Groups A and B, respectively. However, more adverse effects tended to arise in patients who received vancomycin in nephrotoxicity (14.0% and 11.8%, in Groups C and D, respectively.Conclusion: These results suggest that the 2-day regimens with total 1800 mg achieved the most effective therapeutic trough plasma concentration of teicoplanin (20 mg/L. However, 15–20

  9. Relevance of histamine and tryptase concentrations in nasal secretions after nasal challenges with phosphate buffered saline and allergen

    Directory of Open Access Journals (Sweden)

    D. Wang

    1995-01-01

    Full Text Available In this prospective study, a quantitative determination of histamine and tryptase in nasal secretions after nasal phosphate buffered saline (PBS and allergen challenge was performed in 18 atopic patients who were compared with ten non-allergic healthy volunteers. The aim of the study was to determine the normal and pathological concentrations of these important mediators in nasal secretions. The second objective was to test the relevance of these two mast cell secreted mediators after nasal challenge. Results showed that the concentrations of tryptase in almost all samples were under the minimal detection limit (< 0.5 μU/g and only a sigrtificant increase of tryptase (median, 28 μU/g occurred immediately after nasal allergen challenge in the patient group. Histamine concentration significantly increased after every nasal PBS challenge (median, 69 ng/g after first PBS challenge and 165 ng/g after second PBS challenge in the control group, as well as in the patient group after both PBS (median, 69 ng/g and allergen (median, 214 ng/g challenge. On the other hand, a rapid onset of sneezing and increase in nasal airway resistance was experienced only in the patient group after nasal allergen challenge, but did not occur after PBS challenge even though the histamine concentrations significantly increased in both groups. This study suggests that tryptase is a more preferable marker than histamine in quantitative monitoring of mast cell activation especially during the early phase nasal allergic reaction.

  10. Handheld Device Adapted to Smartphone Cameras for the Measurement of Sodium Ion Concentrations at Saliva-Relevant Levels via Fluorescence

    Directory of Open Access Journals (Sweden)

    Michelle Lipowicz

    2015-06-01

    Full Text Available The use of saliva sampling as a minimally-invasive means for drug testing and monitoring physiology is a subject of great interest to researchers and clinicians. This study describes a new optical method based on non-axially symmetric focusing of light using an oblate spheroid sample chamber. The device is simple, lightweight, low cost and is easily attached to several different brands/models of smartphones (Apple, Samsung, HTC and Nokia for the measurement of sodium ion levels at physiologically-relevant saliva concentrations. The sample and fluorescent reagent solutions are placed in a specially-designed, lightweight device that excludes ambient light and concentrates 470-nm excitation light, from a low-power photodiode, within the sample through non-axially-symmetric refraction. The study found that smartphone cameras and post-image processing quantitated sodium ion concentration in water over the range of 0.5–10 mM, yielding best-fit regressions of the data that agree well with a data regression of microplate luminometer results. The data suggest that fluorescence can be used for the measurement of salivary sodium ion concentrations in low-resource or point-of-care settings. With further fluorescent assay testing, the device may find application in a variety of enzymatic or chemical assays.

  11. Interactions of AChE with Aβ Aggregates in Alzheimer’s Brain: Therapeutic Relevance of IDN 5706

    Directory of Open Access Journals (Sweden)

    Francisco Javier Carvajal

    2011-09-01

    Full Text Available Acetylcholinesterase (AChE; EC 3.1.1.7 plays a crucial role in the rapid hydrolysis of the neurotransmitter acetylcholine, in the central and peripheral nervous system and might also participate in non-cholinergic mechanism related to neurodegenerative diseases. Alzheimer’s disease (AD is a neurodegenerative disorder characterized by a progressive deterioration of cognitive abilities, amyloid-β peptide (Aβ accumulation and synaptic alterations. We have previously shown that AChE is able to accelerate the Aβ peptide assembly into Alzheimer-type aggregates increasing its neurotoxicity. Furthermore, AChE activity is altered in brain and blood of Alzheimer’s patients. The enzyme associated to amyloid plaques changes its enzymatic and pharmacological properties, as well as, increases its resistant to low pH, inhibitors and excess of substrate. Here, we reviewed the effects of IDN 5706, a hyperforin derivative that has potential preventive effects on the development of AD. Our results show that treatment with IDN5706 for 10 weeks increases brain AChE activity in seven month-old double transgenic mice (APPswe - PS1 and decreases the content of AChE associated with different types of amyloid plaques in this Alzheimer’s model. We concluded that early treatment with IDN 5706 decreases AChE-Aβ interaction and this effect might be of therapeutic interest in the treatment of AD.

  12. Out-of-Field Dose Equivalents Delivered by Passively Scattered Therapeutic Proton Beams for Clinically Relevant Field Configurations

    International Nuclear Information System (INIS)

    Wroe, Andrew; Clasie, Ben; Kooy, Hanne; Flanz, Jay; Schulte, Reinhard; Rosenfeld, Anatoly

    2009-01-01

    Purpose: Microdosimetric measurements were performed at Massachusetts General Hospital, Boston, MA, to assess the dose equivalent external to passively delivered proton fields for various clinical treatment scenarios. Methods and Materials: Treatment fields evaluated included a prostate cancer field, cranial and spinal medulloblastoma fields, ocular melanoma field, and a field for an intracranial stereotactic treatment. Measurements were completed with patient-specific configurations of clinically relevant treatment settings using a silicon-on-insulator microdosimeter placed on the surface of and at various depths within a homogeneous Lucite phantom. The dose equivalent and average quality factor were assessed as a function of both lateral displacement from the treatment field edge and distance downstream of the beam's distal edge. Results: Dose-equivalent value range was 8.3-0.3 mSv/Gy (2.5-60-cm lateral displacement) for a typical prostate cancer field, 10.8-0.58 mSv/Gy (2.5-40-cm lateral displacement) for the cranial medulloblastoma field, 2.5-0.58 mSv/Gy (5-20-cm lateral displacement) for the spinal medulloblastoma field, and 0.5-0.08 mSv/Gy (2.5-10-cm lateral displacement) for the ocular melanoma field. Measurements of external field dose equivalent for the stereotactic field case showed differences as high as 50% depending on the modality of beam collimation. Average quality factors derived from this work ranged from 2-7, with the value dependent on the position within the phantom in relation to the primary beam. Conclusions: This work provides a valuable and clinically relevant comparison of the external field dose equivalents for various passively scattered proton treatment fields

  13. Sourcing of an alternative pericyte-like cell type from peripheral blood in clinically relevant numbers for therapeutic angiogenic applications.

    Science.gov (United States)

    Blocki, Anna; Wang, Yingting; Koch, Maria; Goralczyk, Anna; Beyer, Sebastian; Agarwal, Nikita; Lee, Michelle; Moonshi, Shehzahdi; Dewavrin, Jean-Yves; Peh, Priscilla; Schwarz, Herbert; Bhakoo, Kishore; Raghunath, Michael

    2015-03-01

    Autologous cells hold great potential for personalized cell therapy, reducing immunological and risk of infections. However, low cell counts at harvest with subsequently long expansion times with associated cell function loss currently impede the advancement of autologous cell therapy approaches. Here, we aimed to source clinically relevant numbers of proangiogenic cells from an easy accessible cell source, namely peripheral blood. Using macromolecular crowding (MMC) as a biotechnological platform, we derived a novel cell type from peripheral blood that is generated within 5 days in large numbers (10-40 million cells per 100 ml of blood). This blood-derived angiogenic cell (BDAC) type is of monocytic origin, but exhibits pericyte markers PDGFR-β and NG2 and demonstrates strong angiogenic activity, hitherto ascribed only to MSC-like pericytes. Our findings suggest that BDACs represent an alternative pericyte-like cell population of hematopoietic origin that is involved in promoting early stages of microvasculature formation. As a proof of principle of BDAC efficacy in an ischemic disease model, BDAC injection rescued affected tissues in a murine hind limb ischemia model by accelerating and enhancing revascularization. Derived from a renewable tissue that is easy to collect, BDACs overcome current short-comings of autologous cell therapy, in particular for tissue repair strategies.

  14. Behavior toxicity to Caenorhabditis elegans transferred to the progeny after exposure to sulfamethoxazole at environmentally relevant concentrations

    Institute of Scientific and Technical Information of China (English)

    Zhenyang Yu; Lei Jiang; Daqiang Yin

    2011-01-01

    Sulfamethoxazole (SMX) is one of the most common detected antibiotics in the environment. In order to study whether SMX can affect behavior and growth and whether these effects could be transferred to the progeny, Caenorhabditis elegans was exposed at environmentally relevant concentrations for 24, 48, 72 and 96 hr, respectively. After exposure, the exposed parent generation (Po) was measured for behavior and growth indicators, which were presented as percentage of controls (POC). Then their corresponding unexposed progeny (F1) was separated and measured for the same indicators. The lowest POC for Po after 96 hr-exposure at 100 mg/L were 37.8%, 12.7%, 45.8% and 70.1% for body bending frequency (BBF), reversal movement (RM), Omega turns (OT) and body length (BL), respectively. And F1 suffered defects with the lowest POC as 55.8%, 24.1%, 48.5% and 60.7% for BBF, RM, OT and BL, respectively. Defects in both Po and F1 showed a time- and concentration-dependent fashion and behavior indicators showed better sensitivity than growth indicator. The observed effects on F1 demonstrated the transferable properties of SMX. Defects of SMX at environmental concentrations suggested that it is necessary to perform further systematical studies on its ecological risk in actual conditions.

  15. Assessment of health status of oysters (Crassostreagigas) exposed to environmentally relevant concentrations of Ag and Cu in brackish waters

    Science.gov (United States)

    Rementeria, Ane; Mikolaczyk, Mathilde; Peña, Ainhize; Lanceleur, Laurent; Blanc, Gérard; Soto, Manu; Schäfer, Jörg; Zaldibar, Beñat

    2017-12-01

    Human activities have altered estuarine environments leading to increased presence of different pollutants including metals. Although the implementation of new environmental policies has caused a considerable decrease in trace metal concentrations in estuaries around the Bay of Biscay, some elements such as copper (Cu) and silver (Ag) are still present in relatively high concentrations. Oysters have been widely used in environmental biomonitoring programs as sentinel organisms. Oysters Crassostrea gigas from an uncontaminated estuary were exposed to sublethal, environmentally relevant concentrations of Cu (2000 ng Cu/L) and Ag (500 ng Ag/L) during 14 days in brackish water (S = 18). A battery of cell and tissue level (exposure) biomarkers at different levels of biological complexity was applied and integrated into the Integrative Biological Response (IBR) index including: metallothionein contents, intralysosomal metal accumulation, digestive gland atrophy and digestive gland tissue integrity. Condition Index (CI) was incorporated into the IBR index as a complementary parameter that reflects the general physiological condition of oysters (organism level). Results indicated an increase in intralysosomal metal accumulation after 7 and 14 days of exposure to Ag together with an increase in the digestive epithelium atrophy and lipofuscin content after 7 days of exposure to Ag. The responses detected with the aid of biomarkers integrated in the IBR index showed higher toxicity in oysters exposed to Ag, inducing the clear onset of detoxification processes which also occurred, to a lower extent, in Cu-exposed oysters.

  16. The effects of therapeutic concentrations ofamisulpride andrisperidone on human plasma lipid peroxidation – invitro studies

    Directory of Open Access Journals (Sweden)

    Anna Dietrich-Muszalska

    2011-09-01

    Full Text Available Introduction: Antipsychotics may in different ways affect the oxidative stress measured by plasma lipid peroxidation. Probably some of them may intensify the oxidative balance disturbances occurring in schizophrenia. The effects of amisulpride and risperidone on redox processes are not known sufficiently yet. Aim of the study: Establishment of the effects of amisulpride and risperidone on human plasma lipid peroxidation measured by determination of the level of thiobarbituric acid-reactive substances (TBARS, in vitro. Material and methods: Blood for the studies was collected from healthy volunteers (aged 24-26 years for ACD solution. Active substances of the examined drugs were dissolved in 0.01% dimethylsulfoxide (DMSO to the final concentrations (of amisulpride 578 ng/ml and risperidone 64 ng/ml and incubated with plasma for 1 and 24 hours at 37ºC. For each experiment the control samples of plasma with DMSO (without the drug were performed. The lipid peroxidation level was measured in plasma by determining the TBARS concentration, using the spectrophotometric method (acc. to Rice-Evans, 1991. The results were analysed using the following statistical methods: the paired Student t-test and ANOVA II variance analysis and NIR test (StatSoft Inc., Statistica v. 6.0. Results: The ANOVA II variance analysis indicated significant differences in the effects of both drugs on TBARS level (F=4.26; df=2, p0.05. Conclusion: Amisulpride and risperidone in concentrations corresponding to doses recommended for treatment of acute episode of schizophrenia do not induce oxidative stress measured by lipid peroxidation. Unlike risperidone, amisulpride exhibits antioxidative effects.

  17. An electron microscopy based method for the detection and quantification of nanomaterial number concentration in environmentally relevant media

    Energy Technology Data Exchange (ETDEWEB)

    Prasad, A. [School of Geography, Earth and Environmental Sciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom); Lead, J.R., E-mail: jlead@mailbox.sc.edu [School of Geography, Earth and Environmental Sciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom); Center for Environmental Nanoscience and Risk, Department of Environmental Health Sciences, Arnold School of Public Health, University South Carolina, Columbia 29208, SC (United States); Baalousha, M., E-mail: mbaalous@mailbox.sc.edu [Center for Environmental Nanoscience and Risk, Department of Environmental Health Sciences, Arnold School of Public Health, University South Carolina, Columbia 29208, SC (United States)

    2015-12-15

    Improved detection and characterization of nanomaterials (NMs) in complex environmental media requires the development of novel sampling approaches to improve the detection limit to be close to environmentally realistic concentrations. Transmission electron microscopy (TEM) is an indispensable metrological tool in nanotechnology and environmental nanoscience due to its high spatial resolution and analytical capabilities when coupled to spectroscopic techniques. However, these capabilities are hampered by the conventional sample preparation methods, which suffer from low NM recovery. The current work presents a validated, fully quantitative sampling technique for TEM that overcomes conventional sample preparation shortcomings, and thus enables the use of TEM for measurement of particle number concentration and their detection in complex media at environmentally realistic concentrations. This sampling method is based on ultracentrifugation of NMs from suspension onto a poly-L-lysine (PLL) functionalized TEM grid, using active deposition (by ultracentrifugation) and retention (by PLL interactions with NM surface) of NMs on the substrate, enabling fully quantitative analysis. Similar analysis with AFM was satisfactory in simple media but the lack of chemical-selectivity of AFM limits its applicability for the detection of NMs in complex environmental samples. The sampling approach was validated using both citrate- and PVP-coated AuNMs in pure water, which demonstrated an even distribution of NM on the TEM grid and high NM recovery (80–100%) at environmentally relevant NM concentrations (ca. 0.20–100 μg L{sup −1}). The applicability of the sampling method to complex environmental samples was demonstrated by the quantification of particle number concentration of AuNMs in EPA soft water (with and without Suwannee River fulvic acid) and lake water. This sample preparation approach is also applicable to other types of NMs with some modifications (e.g. centrifugation

  18. An electron microscopy based method for the detection and quantification of nanomaterial number concentration in environmentally relevant media

    International Nuclear Information System (INIS)

    Prasad, A.; Lead, J.R.; Baalousha, M.

    2015-01-01

    Improved detection and characterization of nanomaterials (NMs) in complex environmental media requires the development of novel sampling approaches to improve the detection limit to be close to environmentally realistic concentrations. Transmission electron microscopy (TEM) is an indispensable metrological tool in nanotechnology and environmental nanoscience due to its high spatial resolution and analytical capabilities when coupled to spectroscopic techniques. However, these capabilities are hampered by the conventional sample preparation methods, which suffer from low NM recovery. The current work presents a validated, fully quantitative sampling technique for TEM that overcomes conventional sample preparation shortcomings, and thus enables the use of TEM for measurement of particle number concentration and their detection in complex media at environmentally realistic concentrations. This sampling method is based on ultracentrifugation of NMs from suspension onto a poly-L-lysine (PLL) functionalized TEM grid, using active deposition (by ultracentrifugation) and retention (by PLL interactions with NM surface) of NMs on the substrate, enabling fully quantitative analysis. Similar analysis with AFM was satisfactory in simple media but the lack of chemical-selectivity of AFM limits its applicability for the detection of NMs in complex environmental samples. The sampling approach was validated using both citrate- and PVP-coated AuNMs in pure water, which demonstrated an even distribution of NM on the TEM grid and high NM recovery (80–100%) at environmentally relevant NM concentrations (ca. 0.20–100 μg L"−"1). The applicability of the sampling method to complex environmental samples was demonstrated by the quantification of particle number concentration of AuNMs in EPA soft water (with and without Suwannee River fulvic acid) and lake water. This sample preparation approach is also applicable to other types of NMs with some modifications (e.g. centrifugation

  19. Sleep-time blood pressure: prognostic value and relevance as a therapeutic target for cardiovascular risk reduction.

    Science.gov (United States)

    Hermida, Ramón C; Ayala, Diana E; Fernández, José R; Mojón, Artemio

    2013-03-01

    showed that the asleep systolic BP mean was the most significant predictor of both total CVD events and major CVD events (a composite of CVD death, myocardial infarction, and stroke). Moreover, when the asleep BP mean was adjusted by the awake mean, only the former was a significant independent predictor of outcome in a Cox proportional-hazard model adjusted for sex, age, diabetes, anemia, and chronic kidney disease. Analyses of changes in ambulatory BP during follow-up revealed 17% reduction in CVD risk for each 5 mm Hg decrease in the asleep systolic BP mean (p < .001), independent of changes in any other clinic or ambulatory BP parameter. The increased event-free survival associated with the progressive reduction in the asleep systolic BP mean during follow-up was significant for subjects with either normal or elevated BP at baseline. The ABPM-derived asleep BP mean was the most significant prognostic marker of CVD morbidity and mortality. Most important, the progressive decrease in asleep BP mean, a novel therapeutic target that requires proper patient evaluation by ABPM and best achieved by ingestion of at least one hypertension medication at bedtime, was the most significant predictor of event-free survival.

  20. Environmentally relevant concentrations of polyethylene microplastics negatively impact the survival, growth and emergence of sediment-dwelling invertebrates.

    Science.gov (United States)

    Ziajahromi, Shima; Kumar, Anupama; Neale, Peta A; Leusch, Frederic D L

    2018-05-01

    Microplastics are a widespread environmental pollutant in aquatic ecosystems and have the potential to eventually sink to the sediment, where they may pose a risk to sediment-dwelling organisms. While the impacts of exposure to microplastics have been widely reported for marine biota, the effects of microplastics on freshwater organisms at environmentally realistic concentrations are largely unknown, especially for benthic organisms. Here we examined the effects of a realistic concentration of polyethylene microplastics in sediment on the growth and emergence of a freshwater organism Chironomus tepperi. We also assessed the influence of microplastic size by exposing C. tepperi larvae to four different size ranges of polyethylene microplastics (1-4, 10-27, 43-54 and 100-126 μm). Exposure to an environmentally relevant concentration of microplastics, 500 particles/kg sediment , negatively affected the survival, growth (i.e. body length and head capsule) and emergence of C. tepperi. The observed effects were strongly dependent on microplastic size with exposure to particles in the size range of 10-27 μm inducing more pronounced effects. While growth and survival of C. tepperi were not affected by the larger microplastics (100-126 μm), a significant reduction in the number of emerged adults was observed after exposure to the largest microplastics, with the delayed emergence attributed to exposure to a stressor. While scanning electron microscopy showed a significant reduction in the size of the head capsule and antenna of C. tepperi exposed to microplastics in the 10-27 μm size range, no deformities to the external structure of the antenna and mouth parts in organisms exposed to the same size range of microplastics were observed. These results indicate that environmentally relevant concentrations of microplastics in sediment induce harmful effects on the development and emergence of C. tepperi, with effects greatly dependent on particle size. Copyright

  1. Enrofloxacin at environmentally relevant concentrations enhances uptake and toxicity of cadmium in the earthworm Eisenia fetida in farm soils

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yinsheng, E-mail: yinshengli@sjtu.edu.cn [School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240 (China); Tang, Hao; Hu, Yingxiu; Wang, Xiuhong; Ai, Xiaojie; Tang, Li [School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240 (China); Matthew, Cory [Institute of Agriculture & Environment, Massey University, Private Bag 11-222, Palmerston North 4442 (New Zealand); Cavanagh, Jo [Landcare Research, PO Box 40, Lincoln 7640 (New Zealand); Qiu, Jiangping [School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240 (China)

    2016-05-05

    Highlights: • Enrofloxacin (EF) and cadmium (Cd) were independently adsorbed in soils. • EF accelerated and increased Cd bioaccumulation in earthworms. • At high concentration EF (10 mg kg{sup −1}) was toxic to earthworms. • EF enhanced Cd induced oxidative stress, and increased burrowing and respiration. • EF did not affect the Cd induced increase in metallothionein in earthworms. - Abstract: Individual and combined effects of enrofloxacin (EF) and cadmium (Cd) on the earthworm Eisenia fetida at environmentally relevant concentrations were investigated. EF is a veterinary antibiotic; Cd is an impurity in phosphatic fertiliser. For both, residues may accumulate in farm soils. In laboratory tests, over 98% of spiked EF was adsorbed by farm soils, with a half-life >8 weeks. However, earthworms absorbed less than 20% of spiked EF. Earthworms in soil with EF concentration 10 mg kg{sup −1} soil experienced transient oxidative stress and exhibited reduced burrowing activity and respiration after an 8-week exposure; EF at 0.1 and 1.0 mg kg{sup −1} soil did not elicit toxicity symptoms. When both were added, Cd did not affect EF uptake, but each increment of spiked EF increased Cd bioaccumulation and associated oxidative stress of earthworms, and also caused decreased burrow length and CO{sub 2} production. However, metallothionein induction was not affected. The enhanced toxicity of Cd to earthworms in the presence of EF at low environmental concentrations may have implications for the health and reproductive success of earthworm populations and highlights the importance of understanding effects of antibiotic contamination of farm soils, and of awareness of environmental effects from interaction between multiple contaminants.

  2. Enrofloxacin at environmentally relevant concentrations enhances uptake and toxicity of cadmium in the earthworm Eisenia fetida in farm soils

    International Nuclear Information System (INIS)

    Li, Yinsheng; Tang, Hao; Hu, Yingxiu; Wang, Xiuhong; Ai, Xiaojie; Tang, Li; Matthew, Cory; Cavanagh, Jo; Qiu, Jiangping

    2016-01-01

    Highlights: • Enrofloxacin (EF) and cadmium (Cd) were independently adsorbed in soils. • EF accelerated and increased Cd bioaccumulation in earthworms. • At high concentration EF (10 mg kg"−"1) was toxic to earthworms. • EF enhanced Cd induced oxidative stress, and increased burrowing and respiration. • EF did not affect the Cd induced increase in metallothionein in earthworms. - Abstract: Individual and combined effects of enrofloxacin (EF) and cadmium (Cd) on the earthworm Eisenia fetida at environmentally relevant concentrations were investigated. EF is a veterinary antibiotic; Cd is an impurity in phosphatic fertiliser. For both, residues may accumulate in farm soils. In laboratory tests, over 98% of spiked EF was adsorbed by farm soils, with a half-life >8 weeks. However, earthworms absorbed less than 20% of spiked EF. Earthworms in soil with EF concentration 10 mg kg"−"1 soil experienced transient oxidative stress and exhibited reduced burrowing activity and respiration after an 8-week exposure; EF at 0.1 and 1.0 mg kg"−"1 soil did not elicit toxicity symptoms. When both were added, Cd did not affect EF uptake, but each increment of spiked EF increased Cd bioaccumulation and associated oxidative stress of earthworms, and also caused decreased burrow length and CO_2 production. However, metallothionein induction was not affected. The enhanced toxicity of Cd to earthworms in the presence of EF at low environmental concentrations may have implications for the health and reproductive success of earthworm populations and highlights the importance of understanding effects of antibiotic contamination of farm soils, and of awareness of environmental effects from interaction between multiple contaminants.

  3. Regulation of NF-κB activity in astrocytes: effects of flavonoids at dietary-relevant concentrations

    International Nuclear Information System (INIS)

    Spilsbury, Alison; Vauzour, David; Spencer, Jeremy P.E.; Rattray, Marcus

    2012-01-01

    Highlights: ► We tested the hypothesis that low concentrations of flavonoids inhibit NF-κB in astrocytes. ► Primary cultured astrocytes possess a functional κB-system, measured using luciferase assays. ► Seven flavonoids (100 nM–1 μM) failed to reduce NF-κB activity in astrocytes. ► Four flavonoids (100 nM–1 μM) failed to reduce TNFa-stimulated NF-κB activity in astrocytes. ► (−)-Epicatechin did not regulate nuclear translocation of the NF-κB subunit, p65. -- Abstract: Neuroinflammation plays an important role in the progression of neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. Sustained activation of nuclear transcription factor κB (NF-κB) is thought to play an important role in the pathogenesis of neurodegenerative disorders. Flavonoids have been shown to possess antioxidant and anti-inflammatory properties and we investigated whether flavonoids, at submicromolar concentrations relevant to their bioavailability from the diet, were able to modulate NF-κB signalling in astrocytes. Using luciferase reporter assays, we found that tumour necrosis factor (TNFα, 150 ng/ml) increased NF-κB-mediated transcription in primary cultures of mouse cortical astrocytes, which was abolished on co-transfection of a dominant-negative IκBα construct. In addition, TNFα increased nuclear localisation of p65 as shown by immunocytochemistry. To investigate potential flavonoid modulation of NF-κB activity, astrocytes were treated with flavonoids from different classes; flavan-3-ols ((−)-epicatechin and (+)-catechin), flavones (luteolin and chrysin), a flavonol (kaempferol) or the flavanones (naringenin and hesperetin) at dietary-relevant concentrations (0.1–1 μM) for 18 h. None of the flavonoids modulated constitutive or TNFα-induced NF-κB activity. Therefore, we conclude that NF-κB signalling in astrocytes is not a major target for flavonoids.

  4. Regulation of NF-{kappa}B activity in astrocytes: effects of flavonoids at dietary-relevant concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Spilsbury, Alison [Reading School of Pharmacy, University of Reading, Reading RG6 6UB (United Kingdom); Vauzour, David; Spencer, Jeremy P.E. [Molecular Nutrition Group, Centre for Integrative Neuroscience and Neurodynamics, School of Chemistry, Food and Pharmacy, University of Reading, Reading RG6 6AP (United Kingdom); Rattray, Marcus, E-mail: m.a.n.rattray@reading.ac.uk [Reading School of Pharmacy, University of Reading, Reading RG6 6UB (United Kingdom)

    2012-02-17

    Highlights: Black-Right-Pointing-Pointer We tested the hypothesis that low concentrations of flavonoids inhibit NF-{kappa}B in astrocytes. Black-Right-Pointing-Pointer Primary cultured astrocytes possess a functional {kappa}B-system, measured using luciferase assays. Black-Right-Pointing-Pointer Seven flavonoids (100 nM-1 {mu}M) failed to reduce NF-{kappa}B activity in astrocytes. Black-Right-Pointing-Pointer Four flavonoids (100 nM-1 {mu}M) failed to reduce TNFa-stimulated NF-{kappa}B activity in astrocytes. Black-Right-Pointing-Pointer (-)-Epicatechin did not regulate nuclear translocation of the NF-{kappa}B subunit, p65. -- Abstract: Neuroinflammation plays an important role in the progression of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Sustained activation of nuclear transcription factor {kappa}B (NF-{kappa}B) is thought to play an important role in the pathogenesis of neurodegenerative disorders. Flavonoids have been shown to possess antioxidant and anti-inflammatory properties and we investigated whether flavonoids, at submicromolar concentrations relevant to their bioavailability from the diet, were able to modulate NF-{kappa}B signalling in astrocytes. Using luciferase reporter assays, we found that tumour necrosis factor (TNF{alpha}, 150 ng/ml) increased NF-{kappa}B-mediated transcription in primary cultures of mouse cortical astrocytes, which was abolished on co-transfection of a dominant-negative I{kappa}B{alpha} construct. In addition, TNF{alpha} increased nuclear localisation of p65 as shown by immunocytochemistry. To investigate potential flavonoid modulation of NF-{kappa}B activity, astrocytes were treated with flavonoids from different classes; flavan-3-ols ((-)-epicatechin and (+)-catechin), flavones (luteolin and chrysin), a flavonol (kaempferol) or the flavanones (naringenin and hesperetin) at dietary-relevant concentrations (0.1-1 {mu}M) for 18 h. None of the flavonoids modulated constitutive or

  5. Incidence of milrinone blood levels outside the therapeutic range and their relevance in children after cardiac surgery for congenital heart disease.

    Science.gov (United States)

    Garcia Guerra, Gonzalo; Joffe, Ari R; Senthilselvan, Ambikaipakan; Kutsogiannis, Demetrios J; Parshuram, Christopher S

    2013-05-01

    To evaluate whether variability in milrinone blood levels (MBL) occurs during administration to critically ill children after surgical repair of congenital heart disease, and the clinical relevance of this variability. Prospective cohort study conducted in the pediatric intensive care unit of a tertiary care teaching and referral hospital. MBL were measured at three time periods after starting milrinone infusion (9-12, 18-24, 40-48 h) and at the end of the infusion. MBL were categorized as within (100-300 ng/ml) or outside the therapeutic range. Low cardiac output syndrome was defined by elevation of either lactate (>2 mmol/l) or arteriovenous oxygen difference (>30%). Five other clinical outcomes were evaluated. Regression analyses evaluated the relationships between MBL and outcomes. Sixty-three patients were included with a total of 220 MBL. Quantification of MBL was by high-performance liquid chromatography. Overall, 114 (52%) MBL were outside the therapeutic range: 78 (36%) subtherapeutic, and 36 (16%) supratherapeutic. Repeated-measures analysis found a significant association between supratherapeutic MBL and low cardiac output syndrome (p = 0.02), and supratherapeutic MBL were associated with arterial-central venous oxygen saturation difference >30% at time 3 (p = 0.007). In this cohort, nontherapeutic MBL were common. Further investigation of milrinone dosing recommendations may improve the postoperative outcomes of children.

  6. The progestin norethisterone affects thyroid hormone-dependent metamorphosis of Xenopus laevis tadpoles at environmentally relevant concentrations.

    Science.gov (United States)

    Lorenz, Claudia; Krüger, Angela; Schöning, Viola; Lutz, Ilka

    2018-04-15

    Previously, levonorgestrel (LNG) has been shown to be an endocrine disruptor of the amphibian thyroid system. In the present study, we investigated whether anti-thyroidal effects are a common property of progestins other than LNG. Premetamorphic Xenopus laevis tadpoles were exposed to norethisterone (NET) and dienogest DIE (each at 0.1-10nM) and LNG (10nM) until completion of metamorphosis. LNG and NET at all concentrations caused a significant developmental retardation whereas DIE did not impair time to metamorphosis. In LNG and 10nM NET exposed animals, tsh mRNA levels increased considerably later than the developmental delay occurred and thyroid histopathology showed no signs of TSH-hyperstimulation. Instead, thyroid glands from these treatments appeared inactive in producing thyroid hormones. Thyroidal transcript levels of dio2 and dio3 were increased by treatments with LNG and NET at 1nM and 10nM, whereas iyd mRNA was reduced by LNG and 10nM NET. Expression of slc5α5 was not changed by any treatment. Effects of DIE differed from those induced by LNG and NET. No developmental delay was measurable; however, tshβ and dio2 mRNAs were increased in pituitary glands of tadpoles exposed to 1.0nM and 10nM DIE. Thyroid histopathology displayed no abnormalities and thyroidal mRNA expression of the genes analyzed (slc5α5, iyd, dio2, dio3) was not changed by DIE. Overall, our results provide evidence that the anti-thyroidal effects already known from LNG are also present in another progestin, namely NET, even at environmentally relevant concentrations. In conclusion we suggest that progestins do not only pose an environmental risk in terms of their impact on reproductive success of aquatic vertebrates, but also with respect to their anti-thyroidal properties affecting amphibian metamorphosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Salt at concentrations relevant to meat processing enhances Shiga toxin 2 production in Escherichia coli O157:H7.

    Science.gov (United States)

    Harris, Shaun M; Yue, Wan-Fu; Olsen, Sarena A; Hu, Jia; Means, Warrie J; McCormick, Richard J; Du, Min; Zhu, Mei-Jun

    2012-10-15

    Escherichia coli (E. coli) O157:H7 remains a major food safety concern associated with meat, especially beef products. Shiga toxins (Stx) are key virulence factors produced by E. coli O157:H7 that are responsible for hemorrhagic colitis and Hemolytic Uremic Syndrome. Stx are heat stable and can be absorbed after oral ingestion. Despite the extensive study of E. coli O157:H7 survival during meat processing, little attention is paid to the production of Stx during meat processing. The objective of this study was to elucidate the effect of salt, an essential additive to processed meat, at concentrations relevant to meat processing (0%, 1%, 2%, 3%, W/V) on Stx2 production and Stx2 prophage induction by E. coli O157:H7 strains. For both E. coli O157:H7 86-24 and EDL933 strains, including 2% salt in LB broth decreased (Pmeat processing enhances Stx production, a process linked to bacterial stress response and lambdoid prophage induction. Published by Elsevier B.V.

  8. The landsnail Cepaea nemoralis regulates internal Cd levels when fed on Cd-enriched stinging nettle (Urtica dioica) leaves at low, field-relevant concentrations.

    NARCIS (Netherlands)

    Notten, M.J.M.; Oosthoek, A.; Rozema, J.; Aerts, R.

    2006-01-01

    We studied Cd accumulation in Cepaea nemoralis snails at low, but field-relevant Cd concentrations in the diet (Urtica dioica leaves). Six treatments of U. dioica plants were grown, resulting in leaf Cd concentrations between 0 and 2.6 μg g

  9. Population pharmacokinetics of piperacillin in the early phase of septic shock: does standard dosing result in therapeutic plasma concentrations?

    Science.gov (United States)

    Öbrink-Hansen, Kristina; Juul, Rasmus Vestergaard; Storgaard, Merete; Thomsen, Marianne Kragh; Hardlei, Tore Forsingdal; Brock, Birgitte; Kreilgaard, Mads; Gjedsted, Jakob

    2015-11-01

    Antibiotic dosing in septic shock patients poses a challenge for clinicians due to the pharmacokinetic (PK) variability seen in this patient population. Piperacillin-tazobactam is often used for empirical treatment, and initial appropriate dosing is crucial for reducing mortality. Accordingly, we determined the pharmacokinetic profile of piperacillin (4 g) every 8 h, during the third consecutive dosing interval, in 15 patients treated empirically for septic shock. We developed a population pharmacokinetic model to assess empirical dosing and to simulate alternative dosing regimens and modes of administration. Time above the MIC (T>MIC) predicted for each patient was evaluated against clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/liter). Pharmacokinetic-pharmacodynamic (PK/PD) targets evaluated were 50% fT>4×MIC and 100% fT>MIC. A population PK model was developed using NONMEM, and data were best described by a two-compartment model. Central and intercompartmental clearances were 3.6 liters/h (relative standard error [RSE], 15.7%) and 6.58 liters/h (RSE, 16.4%), respectively, and central and peripheral volumes were 7.3 liters (RSE, 11.8%) and 3.9 liters (RSE, 9.7%), respectively. Piperacillin plasma concentrations varied considerably between patients and were associated with levels of plasma creatinine. Patients with impaired renal function were more likely to achieve predefined PK/PD targets than were patients with preserved or augmented renal function. Simulations of alternative dosing regimens showed that frequent intermittent bolus dosing as well as dosing by extended and continuous infusion increases the probability of attaining therapeutic plasma concentrations. For septic shock patients with preserved or augmented renal function, dose increment or prolonged infusion of the drug needs to be considered. (This study has been registered at ClinicalTrials.gov under registration no. NCT02306928.). Copyright © 2015, American Society for Microbiology

  10. Effects of ABCB1, ABCC2, UGT2B7 and HNF4α genetic polymorphisms on oxcarbazepine concentrations and therapeutic efficacy in patients with epilepsy.

    Science.gov (United States)

    Shen, Chunhong; Zhang, Bijun; Liu, Zhirong; Tang, Yelei; Zhang, Yinxi; Wang, Shan; Guo, Yi; Ding, Yao; Wang, Shuang; Ding, Meiping

    2017-10-01

    The aim of the study is to investigate the effects of ABCB1, ABCC2, UGT2B7 and HNF4α genetic polymorphisms on plasma oxcarbazepine (OXC) concentrations and therapeutic efficacy in Han Chinese patients with epilepsy. We recruited 116 Han Chinese patients with epilepsy who were receiving OXC monotherapy. Blood samples were taken and OXC levels were measured. The polymorphisms of ABCB1 rs1045642, ABCC2 rs2273697, UGT2B7 rs7439366, and HNF4α rs2071197 were determined. The therapeutic efficacy of OXC at the 1-year time-point was assessed. Data analysis was performed using IBM SPSS Statistics 22.0. The genetic polymorphism of ABCB1 rs1045642 was found to be associated with normalized OXC concentration and therapeutic efficacy in patients with epilepsy (P<0.05). As for UGT2B7 rs7439366, the allele polymorphism exhibited a correlation with treatment outcome, but not OXC concentration. The polymorphisms of ABCC2 rs2273697 and HNF4α rs2071197 was not associated with OXC concentrations and therapeutic efficacy. These results suggested that ABCB1 rs1045642 and UGT2B7 rs7439366 may affect OXC pharmacokinetics and therapeutic efficacy in Han Chinese patients with epilepsy. However, further studies in larger populations and other ethnic groups are required. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  11. The landsnail Cepaea nemoralis regulates internal Cd levels when fed on Cd-enriched stinging nettle (Urtica dioica) leaves at low, field-relevant concentrations

    International Nuclear Information System (INIS)

    Notten, M.J.M.; Oosthoek, A.J.P.; Rozema, J.; Aerts, R.

    2006-01-01

    We studied Cd accumulation in Cepaea nemoralis snails at low, but field-relevant Cd concentrations in the diet (Urtica dioica leaves). Six treatments of U. dioica plants were grown, resulting in leaf Cd concentrations between 0 and 2.6 μg g -1 dw. Seven snails per treatment were fed for 38 days. Leaf Cd concentrations did not affect food consumption rates, and consequently Cd intake rates increased with increasing leaf concentrations. No differences were detected among treatments in the final soft tissue Cd concentrations and body burdens in the snails. Regression analyses showed no positive relationship between either snail Cd concentrations or body burdens and total Cd intake. This suggests a regulation of internal Cd concentrations at low food Cd concentrations. Our data suggest that Cd excretion via the mucus plays a substantial role in this regulation, in addition to Cd excretion via the faeces. Snail shells were no sinks for Cd. - Cd excretion via the mucus plays a substantial role in the regulation of C. nemoralis soft tissue Cd concentrations at low, but field-relevant Cd concentrations in the food

  12. The landsnail Cepaea nemoralis regulates internal Cd levels when fed on Cd-enriched stinging nettle (Urtica dioica) leaves at low, field-relevant concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Notten, M.J.M. [Institute of Ecological Science, Department of Systems Ecology, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV, Amsterdam (Netherlands)]. E-mail: martje.notten@ecology.falw.vu.nl; Oosthoek, A.J.P. [Institute of Ecological Science, Department of Systems Ecology, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV, Amsterdam (Netherlands); Rozema, J. [Institute of Ecological Science, Department of Systems Ecology, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV, Amsterdam (Netherlands); Aerts, R. [Institute of Ecological Science, Department of Systems Ecology, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV, Amsterdam (Netherlands)

    2006-01-15

    We studied Cd accumulation in Cepaea nemoralis snails at low, but field-relevant Cd concentrations in the diet (Urtica dioica leaves). Six treatments of U. dioica plants were grown, resulting in leaf Cd concentrations between 0 and 2.6 {mu}g g{sup -1} dw. Seven snails per treatment were fed for 38 days. Leaf Cd concentrations did not affect food consumption rates, and consequently Cd intake rates increased with increasing leaf concentrations. No differences were detected among treatments in the final soft tissue Cd concentrations and body burdens in the snails. Regression analyses showed no positive relationship between either snail Cd concentrations or body burdens and total Cd intake. This suggests a regulation of internal Cd concentrations at low food Cd concentrations. Our data suggest that Cd excretion via the mucus plays a substantial role in this regulation, in addition to Cd excretion via the faeces. Snail shells were no sinks for Cd. - Cd excretion via the mucus plays a substantial role in the regulation of C. nemoralis soft tissue Cd concentrations at low, but field-relevant Cd concentrations in the food.

  13. Effects of nanomolar cadmium concentrations on water plants - comparison of biochemical and biophysical mechanisms of toxicity under environmentally relevant conditions

    OpenAIRE

    Andresen, Elisa

    2014-01-01

    In this thesis, the effects of the highly toxic heavy metal cadmium (Cd) on the rootless aquatic model plant Ceratophyllum demersum are investigated on the biochemical and biophysical level. The experiments were carried out using environmentally relevant conditions, i.e. light and temperature followed a sinusoidal cycle, a low biomass to water ratio resembled the situation in oligotrophic lakes and a continuous exchange of the defined nutrient solution ensured that metal uptake into the plant...

  14. Influence of environmentally relevant concentrations of vinclozolin on quality, DNA integrity, and antioxidant responses of sterlet Acipenser ruthenus spermatozoa.

    Science.gov (United States)

    Gazo, Ievgeniia; Linhartova, Pavla; Shaliutina, Anna; Hulak, Martin

    2013-04-25

    The effects of vinclozolin (VIN), an anti-androgenic fungicide, on quality, oxidative stress, DNA integrity, and ATP level of sterlet (Acipenser ruthenus) spermatozoa were investigated in vitro. Fish spermatozoa were incubated with different concentrations of vinclozolin (0.5, 2, 10, 15, 20 and 50 μg/l) for 2 h. A dose-dependent reduction in spermatozoa motility and velocity was observed at concentrations of 2-50 μg/l. A dramatic increase in DNA fragmentation was recorded at concentrations 10 μg/l and above. After 2 h exposure at higher test concentrations (10-50 μg/l), oxidative stress was apparent, as reflected by significantly higher levels of protein and lipid oxidation and significantly greater superoxide dismutase activity. Intracellular ATP content of spermatozoa decreased with increasing concentrations of VIN. The results demonstrated that VIN can induce reactive oxygen species stress in fish spermatozoa, which could impair the sperm quality, DNA integrity, ATP content, and the antioxidant defense system. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. Bisphenol A induces superfeminization in the ramshorn snail Marisa cornuarietis(Gastropoda: Prosobranchia) at environmentally relevant concentrations.

    Science.gov (United States)

    Oehlmann, Jörg; Schulte-Oehlmann, Ulrike; Bachmann, Jean; Oetken, Matthias; Lutz, Ilka; Kloas, Werner; Ternes, Thomas A

    2006-04-01

    Previous investigations have shown that bisphenol A (BPA) induces a superfeminization syndrome in the freshwater snail Marisa cornuarietis at concentrations as low as 1 microg/L. Superfemales are characterized by the formation of additional female organs, enlarged accessory sex glands, gross malformations of the pallial oviduct, and a stimulation of egg and clutch production, resulting in increased female mortality. However, these studies were challenged on the basis of incomplete experimentation. Therefore, the objective of the current approach was to bridge several gaps in knowledge by conducting additional experiments. In an initial series of experiments, study results from the reproductive phase of the snails were evaluated in the sub-micrograms per liter range. Before and after the spawning season, superfemale responses were observed [NOEC (no observed effect concentration) 7.9 ng/L, EC10 (effective concentration at 10%) 13.9 ng/L], which were absent during the spawning season. A further experiment investigated the temperature dependence of BPA responses by exposing snails at two temperatures in parallel. The adverse effect of BPA was at least partially masked at 27 degrees C (EC10 998 ng/L) when compared with 20 degrees C (EC10 14.8 ng/L). In M. cornuarietis, BPA acts as an estrogen receptor (ER) agonist, because effects were completely antagonized by a co-exposure to tamoxifen and Faslodex. Antiandrogenic effects of BPA, such as a significant decrease in penis length at 20 degrees C, were also observed. Competitive receptor displacement experiments indicate the presence of androgen- and estrogen-specific binding sites. The affinity for BPA of the estrogen binding sites in M. cornuarietis is higher than that of the ER in aquatic vertebrates. The results emphasize that prosobranchs are affected by BPA at lower concentrations than are other wildlife groups, and the findings also highlight the importance of exposure conditions.

  16. Prediction of Adsorption Equilibrium of VOCs onto Hyper-Cross-Linked Polymeric Resin at Environmentally Relevant Temperatures and Concentrations Using Inverse Gas Chromatography.

    Science.gov (United States)

    Jia, Lijuan; Ma, Jiakai; Shi, Qiuyi; Long, Chao

    2017-01-03

    Hyper-cross-linked polymeric resin (HPR) represents a class of predominantly microporous adsorbents and has good adsorption performance toward VOCs. However, adsorption equilibrium of VOCs onto HPR are limited. In this research, a novel method for predicting adsorption capacities of VOCs on HPR at environmentally relevant temperatures and concentrations using inverse gas chromatography data was proposed. Adsorption equilibrium of six VOCs (n-pentane, n-hexane, dichloromethane, acetone, benzene, 1, 2-dichloroethane) onto HPR in the temperature range of 403-443 K were measured by inverse gas chromatography (IGC). Adsorption capacities at environmentally relevant temperatures (293-328 K) and concentrations (P/P s = 0.1-0.7) were predicted using Dubinin-Radushkevich (DR) equation based on Polany's theory. Taking consideration of the swelling properties of HPR, the volume swelling ratio (r) was introduced and r·V micro was used instead of V micro determined by N 2 adsorption data at 77 K as the parameter q 0 (limiting micropore volume) of the DR equation. The results showed that the adsorption capacities of VOCs at environmentally relevant temperatures and concentrations can be predicted effectively using IGC data, the root-mean-square errors between the predicted and experimental data was below 9.63%. The results are meaningful because they allow accurate prediction of adsorption capacities of adsorbents more quickly and conveniently using IGC data.

  17. Effects of Field-Relevant Concentrations of Clothianidin on Larval Development of the Butterfly Polyommatus icarus (Lepidoptera, Lycaenidae).

    Science.gov (United States)

    Basley, Kate; Goulson, Dave

    2018-04-03

    Arable field margins are often sown with wildflowers to encourage pollinators and other beneficial or desirable insects such as bees and butterflies. Concern has been raised that these margins may be contaminated with systemic pesticides such as neonicotinoids used on the adjacent crop, and that this may negatively impact beneficial insects. The use of neonicotinoids has been linked to butterfly declines, and species such as the common blue butterfly ( Polyommatus icarus) that feed upon legumes commonly sown in arable field margins, may be exposed to such toxins. Here, we demonstrate that the larval food plants of P. icarus growing in an arable field margin adjacent to a wheat crop treated with the neonicotinoid clothianidin not only contain the pesticide at concentrations comparable to and sometimes higher than those found in foliage of treated crops (range 0.2-48 ppb) but also remain detectable at these levels for up to 21 months after sowing of the crop. Overall, our study demonstrates that nontarget herbivorous organisms in arable field margins are likely to be chronically exposed to neonicotinoids. Under laboratory conditions, exposure to clothianidin at 15 ppb (a field-realistic dose) or above reduced larval growth for the first 9 days of the experiment. Although there was evidence of clothianidin inducing mortality in larvae, with highest survival in control groups, the dose-response relationship was unclear. Our study suggests that larvae of this butterfly exhibit some deleterious sublethal and sometimes lethal impacts of exposure to clothianidin, but many larvae survive to adulthood even when exposed to high doses.

  18. Environmentally-relevant concentrations of atrazine induce non-monotonic acceleration of developmental rate and increased size at metamorphosis in Rhinella arenarum tadpoles.

    Science.gov (United States)

    Brodeur, Julie C; Sassone, Alina; Hermida, Gladys N; Codugnello, Nadia

    2013-06-01

    Despite of the various studies reporting on the subject, anticipating the impacts of the widely-used herbicide atrazine on anuran tadpoles metamorphosis remains complex as increases or decreases of larval period duration are almost as frequently reported as an absence of effect. The aim of the present study was to examine the effects of environmentally-relevant concentrations of atrazine (0.1, 1, 10, 100, and 1000μg/L) on the timings of metamorphosis and body size at metamorphosis in the common South American toad, Rhinella arenarum (Anura: bufonidae). None of the atrazine concentrations tested significantly altered survival. Low atrazine concentrations in the range of 1-100μg/L were found to accelerate developmental rate in a non-monotonic U-shaped concentration-response relationship. This observed acceleration of the metamorphic process occurred entirely between stages 25 and 39; treated tadpoles proceeding through metamorphosis as control animals beyond this point. Together with proceeding through metamorphosis at a faster rate, tadpoles exposed to atrazine concentrations in the range of 1-100μg/L furthermore transformed into significantly larger metamorphs than controls, the concentration-response curve taking the form of an inverted U in this case. The no observed effect concentration (NOEC) was 0.1μg atrazine/L for both size at metamorphosis and timings of metamorphosis. Tadpoles exposed to 100μg/L 17β-estradiol presented the exact same alterations of developmental rate and body size as those treated with 1, 10 and 100μg/L of atrazine. Elements of the experimental design that facilitated the detection of alterations of metamorphosis at low concentrations of atrazine are discussed, together with the ecological significance of those findings. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Toxicity of TiO2 nanoparticles on soil nitrification at environmentally relevant concentrations: Lack of classical dose-response relationships.

    Science.gov (United States)

    Simonin, Marie; Martins, Jean M F; Le Roux, Xavier; Uzu, Gaëlle; Calas, Aude; Richaume, Agnès

    2017-03-01

    Titanium-dioxide nanoparticles (TiO 2 -NPs) are increasingly released in agricultural soils through, e.g. biosolids, irrigation or nanoagrochemicals. Soils are submitted to a wide range of concentrations of TiO 2 -NPs depending on the type of exposure. However, most studies have assessed the effects of unrealistically high concentrations, and the dose-response relationships are not well characterized for soil microbial communities. Here, using soil microcosms, we assessed the impact of TiO 2 -NPs at concentrations ranging from 0.05 to 500 mg kg -1  dry-soil, on the activity and abundance of ammonia-oxidizing archaea (AOA) and bacteria (AOB), and nitrite-oxidizing bacteria (Nitrobacter and Nitrospira). In addition, aggregation and oxidative potential of TiO 2 -NPs were measured in the spiking suspensions, as they can be important drivers of TiO 2 -NPs toxicity. After 90 days of exposure, non-classical dose-response relationships were observed for nitrifier abundance or activity, making threshold concentrations impossible to compute. Indeed, AOA abundance was reduced by 40% by TiO 2 -NPs whatever the concentration, while Nitrospira was never affected. Moreover, AOB and Nitrobacter abundances were decreased mainly at intermediate concentrations nitrification was reduced by 25% at the lowest (0.05 mg kg -1 ) and the highest (100 and 500 mg kg -1 ) TiO 2 -NPs concentrations. Path analyses indicated that TiO 2 -NPs affected nitrification through an effect on the specific activity of nitrifiers, in addition to indirect effects on nitrifier abundances. Altogether these results point out the need to include very low concentrations of NPs in soil toxicological studies, and the lack of relevance of classical dose-response tests and ecotoxicological dose metrics (EC50, IC50…) for TiO 2 -NPs impact on soil microorganisms.

  20. Population pharmacokinetics of piperacillin in the early phase of septic shock – does standard dosing result in therapeutic plasma concentrations?

    DEFF Research Database (Denmark)

    Öbrink-Hansen, Kristina Margareta; Juul, Rasmus Vestergaard; Storgaard, Merete

    2015-01-01

    using NONMEM and data was best described by a two-compartment model. Central and inter-compartmental clearances were 3.6 L/h (RSE 15.7%) and 6.58 (16.4%), and central and peripheral volumes were 7.3 L (RSE 11.8 %) and 3.9 L (RSE 9.7%), respectively. Piperacillin plasma concentrations varied considerably...

  1. Inhibition of peroxynitrite-mediated DNA strand cleavage and hydroxyl radical formation by aspirin at pharmacologically relevant concentrations: Implications for cancer intervention

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Wei [Division of Biomedical Sciences, Edward Via Virginia College of Osteopathic Medicine, Virginia Tech Corporate Research Center, Blacksburg, VA 24060 (United States); College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310035 (China); Department of Food Science and Technology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 (United States); Zhu, Hong; Jia, Zhenquan [Division of Biomedical Sciences, Edward Via Virginia College of Osteopathic Medicine, Virginia Tech Corporate Research Center, Blacksburg, VA 24060 (United States); Li, Jianrong [College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310035 (China); Misra, Hara P. [Division of Biomedical Sciences, Edward Via Virginia College of Osteopathic Medicine, Virginia Tech Corporate Research Center, Blacksburg, VA 24060 (United States); Zhou, Kequan, E-mail: kzhou@wayne.edu [Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202 (United States); Li, Yunbo, E-mail: yli@vcom.vt.edu [Division of Biomedical Sciences, Edward Via Virginia College of Osteopathic Medicine, Virginia Tech Corporate Research Center, Blacksburg, VA 24060 (United States)

    2009-12-04

    Epidemiological studies have suggested that the long-term use of aspirin is associated with a decreased incidence of human malignancies, especially colorectal cancer. Since accumulating evidence indicates that peroxynitrite is critically involved in multistage carcinogenesis, this study was undertaken to investigate the ability of aspirin to inhibit peroxynitrite-mediated DNA damage. Peroxynitrite and its generator 3-morpholinosydnonimine (SIN-1) were used to cause DNA strand breaks in {phi}X-174 plasmid DNA. We demonstrated that the presence of aspirin at concentrations (0.25-2 mM) compatible with amounts in plasma during chronic anti-inflammatory therapy resulted in a significant inhibition of DNA cleavage induced by both peroxynitrite and SIN-1. Moreover, the consumption of oxygen caused by 250 {mu}M SIN-1 was found to be decreased in the presence of aspirin, indicating that aspirin might affect the auto-oxidation of SIN-1. Furthermore, EPR spectroscopy using 5,5-dimethylpyrroline-N-oxide (DMPO) as a spin trap demonstrated the formation of DMPO-hydroxyl radical adduct (DMPO-OH) from authentic peroxynitrite, and that aspirin at 0.25-2 mM potently diminished the radical adduct formation in a concentration-dependent manner. Taken together, these results demonstrate for the first time that aspirin at pharmacologically relevant concentrations can inhibit peroxynitrite-mediated DNA strand breakage and hydroxyl radical formation. These results may have implications for cancer intervention by aspirin.

  2. Inhibition of peroxynitrite-mediated DNA strand cleavage and hydroxyl radical formation by aspirin at pharmacologically relevant concentrations: Implications for cancer intervention

    International Nuclear Information System (INIS)

    Chen, Wei; Zhu, Hong; Jia, Zhenquan; Li, Jianrong; Misra, Hara P.; Zhou, Kequan; Li, Yunbo

    2009-01-01

    Epidemiological studies have suggested that the long-term use of aspirin is associated with a decreased incidence of human malignancies, especially colorectal cancer. Since accumulating evidence indicates that peroxynitrite is critically involved in multistage carcinogenesis, this study was undertaken to investigate the ability of aspirin to inhibit peroxynitrite-mediated DNA damage. Peroxynitrite and its generator 3-morpholinosydnonimine (SIN-1) were used to cause DNA strand breaks in φX-174 plasmid DNA. We demonstrated that the presence of aspirin at concentrations (0.25-2 mM) compatible with amounts in plasma during chronic anti-inflammatory therapy resulted in a significant inhibition of DNA cleavage induced by both peroxynitrite and SIN-1. Moreover, the consumption of oxygen caused by 250 μM SIN-1 was found to be decreased in the presence of aspirin, indicating that aspirin might affect the auto-oxidation of SIN-1. Furthermore, EPR spectroscopy using 5,5-dimethylpyrroline-N-oxide (DMPO) as a spin trap demonstrated the formation of DMPO-hydroxyl radical adduct (DMPO-OH) from authentic peroxynitrite, and that aspirin at 0.25-2 mM potently diminished the radical adduct formation in a concentration-dependent manner. Taken together, these results demonstrate for the first time that aspirin at pharmacologically relevant concentrations can inhibit peroxynitrite-mediated DNA strand breakage and hydroxyl radical formation. These results may have implications for cancer intervention by aspirin.

  3. A single exposure of sediment sulphate-reducing bacteria to oxytetracycline concentrations relevant to aquaculture enduringly disturbed their activity, abundance and community structure.

    Science.gov (United States)

    Fernández, M L; Granados-Chinchilla, F; Rodríguez, C

    2015-08-01

    Although feed medicated with antibiotics is widely used in animal production to prevent and treat bacterial infections, the effect of these drugs on nontarget anaerobic bacteria is unknown. We aimed to clarify whether a single exposure of sulphate-reducing bacteria (SRB) from a tilapia pond to oxytetracycline (OTC) concentrations relevant to aquaculture impacts their function, abundance and community structure. To demonstrate changes in SO4(2-) content, SRB abundance, dsrB copy number and SRB diversity, sediment mesocosms were spiked with 5, 25, 50 and 75 mg OTC kg(-1) and examined for 30 days by means of ion chromatography, qPCR, cultivation and fluorescent in situ hybridization (FISH). On day 3, we measured higher SO4(2-) concentrations (ca. two-fold) and a reduction in dsrB copy numbers of approximately 50% in the treatments compared to the controls. After 30 days, a subtle yet measurable enrichment of bacteria from the order Desulfovibrionales occurred in mesocosms receiving ≥ 50 mg OTC kg(-1), notwithstanding that SRB counts decreased two orders of magnitude. OTC was dynamically and reversibly converted into 4-epioxytetracycline and other related compounds in a dose-dependent manner during the experiment. A single exposure to rather high OTC concentrations triggered functional and structural changes in a SRB community that manifested quickly and persisted for a month. This study improves our limited knowledge on the ecotoxicology of antibiotics in anaerobic environments. © 2015 The Society for Applied Microbiology.

  4. Trafficking of drug candidates relevant for sports drug testing: detection of non-approved therapeutics categorized as anabolic and gene doping agents in products distributed via the Internet.

    Science.gov (United States)

    Thevis, Mario; Geyer, Hans; Thomas, Andreas; Schänzer, Wilhelm

    2011-05-01

    Identifying the use of non-approved drugs by cheating athletes has been a great challenge for doping control laboratories. This is due to the additional complexities associated with identifying relatively unknown and uncharacterized compounds and their metabolites as opposed to known and well-studied therapeutics. In 2010, the prohibited drug candidates and gene doping substances AICAR and GW1516, together with the selective androgen receptor modulator (SARM) MK-2866 were obtained by the Cologne Doping Control Laboratory from Internet suppliers and their structure, quantity, and formulation elucidated. All three compounds proved authentic as determined by liquid chromatography-high resolution/high accuracy (tandem) mass spectrometry and comparison to reference material. While AICAR was provided as a colourless powder in 100 mg aliquots, GW1516 was obtained as an orange/yellow suspension in water/glycerol (150 mg/ml), and MK-2866 (25 mg/ml) was shipped dissolved in polyethylene glycol (PEG) 300. In all cases, the quantified amounts were considerably lower than indicated on the label. The substances were delivered via courier, with packaging identifying them as containing 'amino acids' and 'green tea extract', arguably to circumvent customs control. Although all of the substances were declared 'for research only', their potential misuse in illicit performance-enhancement cannot be excluded; moreover sports drug testing authorities should be aware of the facile availability of black market copies of these drug candidates. Copyright © 2011 John Wiley & Sons, Ltd.

  5. Relevance analysis and short-term prediction of PM2.5 concentrations in Beijing based on multi-source data

    Science.gov (United States)

    Ni, X. Y.; Huang, H.; Du, W. P.

    2017-02-01

    The PM2.5 problem is proving to be a major public crisis and is of great public-concern requiring an urgent response. Information about, and prediction of PM2.5 from the perspective of atmospheric dynamic theory is still limited due to the complexity of the formation and development of PM2.5. In this paper, we attempted to realize the relevance analysis and short-term prediction of PM2.5 concentrations in Beijing, China, using multi-source data mining. A correlation analysis model of PM2.5 to physical data (meteorological data, including regional average rainfall, daily mean temperature, average relative humidity, average wind speed, maximum wind speed, and other pollutant concentration data, including CO, NO2, SO2, PM10) and social media data (microblog data) was proposed, based on the Multivariate Statistical Analysis method. The study found that during these factors, the value of average wind speed, the concentrations of CO, NO2, PM10, and the daily number of microblog entries with key words 'Beijing; Air pollution' show high mathematical correlation with PM2.5 concentrations. The correlation analysis was further studied based on a big data's machine learning model- Back Propagation Neural Network (hereinafter referred to as BPNN) model. It was found that the BPNN method performs better in correlation mining. Finally, an Autoregressive Integrated Moving Average (hereinafter referred to as ARIMA) Time Series model was applied in this paper to explore the prediction of PM2.5 in the short-term time series. The predicted results were in good agreement with the observed data. This study is useful for helping realize real-time monitoring, analysis and pre-warning of PM2.5 and it also helps to broaden the application of big data and the multi-source data mining methods.

  6. Tacrolimus concentration/dose ratio as a therapeutic drug monitoring strategy: The influence of gender and comedication

    Directory of Open Access Journals (Sweden)

    Rančić Nemanja

    2015-01-01

    Full Text Available Background/Aim. A combination of tacrolimus and other drugs such as corticosteroids has been commonly used immunosuppresive regimens. On the other hand, there is a growing body of evidence that male and female may differ in their response to the equal drug treatment. The aim of the study was to estimated the use of tacrolimus concentration/dose (C/D ratio for the assessment of the influence of gender differences and comedication on tacrolimus exposure in renal transplant recipients. Methods. This prospective case series study included 54 patients, in which the unit of monitoring was outpatient examination (1,872 of the renal transplant patients. The patients were monitored in the period 2010-2014, starting one month after the transplantation. Tacrolimus trough concentrations (TTC were measured by chemiluminescence microparticles immunoassay. Results. TTC and the tacrolimus C/D ratio were significantly lower in the females comparing with the males. Contrary to the males, in the females a significant increase of the tacrolimus daily dose (TDD per body weight and TTC, along with the corticosteroid dose increase, was not accompanied by any significant changes in the tacrolimus C/D ratio; in different corticosteroid doses faster elimination of tacrolimus was found with the exception of the doses > 0.25 mg/kg. In the patients treated with proton pump inhibitors, mainly with pantoprazole TDD per body weight and TTC were significantly higher, while the tacrolimus C/D ratio was significantly lower compared to the patients without this treatment. In the patients treated with calcium channel blockers, TDD per body weight was significantly lower (particularly with amlodipine while the tacrolimus C/D ratio was higher compared to the patients who were not treated by them. Conclusion. A lower tacrolimus exposure was detected in females in comparison to males. When gender differences were considered in the context of different corticosteroid doses, faster

  7. Therapeutic effect of continuous exercise training program on serum creatinine concentration in men with hypertension: a randomized controlled trial.

    Science.gov (United States)

    Sikiru, L; Okoye, G C

    2014-09-01

    Creatinine (Cr) has been implicated as an independent predictor of hypertension and exercise has been reported as adjunct therapy for hypertension. The purpose of the present study was to investigate the effect of continuous training programme on blood pressure and serum creatinine concentration in black African subjects with hypertension. Three hundred and fifty seven male patients with mild to moderate (systolic blood pressure [SBP] between 140-180 & diastolic blood pressure [DBP] between 90-109 mmHg) essential hypertension were age matched and randomly grouped into continuous & control groups. The continuous group involved in an 8 weeks continuous training (60-79% HR reserve) of between 45 minutes to 60 minutes, 3 times per week, while the control group remain sedentary. SBP, DBP, VO2max, serum Cr, body mass index (BMI), waist hip ratio (WHR) and percent (%) body fat. Analysis of covariance (ANCOVA) and Pearson correlation tests were used in data analysis. Findings of the study revealed significant decreased effects of continuous training programme on SBP, DBP, Cr, BMI, WHR, % body fat and significant increase in VO2max at pexercise training as a multi-therapy in the down regulation of blood pressure, serum Cr, body size and body fat in hypertension.

  8. Therapeutic efficacy and safety of various botulinum toxin A doses and concentrations in spastic foot after stroke: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Jiang Li

    2017-01-01

    Full Text Available No recommended guidelines currently exist for the therapeutic concentration or dose of botulinum toxin type A (BTXA injected into the muscle to treat limb spasticity. Therefore, in this randomized controlled trial, we explored the safety and efficacy of two concentrations and two doses of BTXA in the treatment of spastic foot after stroke to optimize this treatment in these patients. Eligible patients (n = 104 were randomized into four groups. The triceps surae and tibialis posterior on the affected side were injected with BTXA at one of two doses (200 U or 400 U and two concentrations (50 U/mL or 100 U/mL. The following assessments were conducted before as well as 4 days and 1, 2, 4, and 12 weeks after treatment: spasticity, assessed using the modified Ashworth scale; basic functional mobility, assessed using a timed up and go test; pace, assessed using a 10-meter timed walking test; and the ability to walk, assessed using Holden's graded scale and a visual analog scale. The reported results are based on the 89 patients that completed the study. We found significant differences for the two doses and concentrations of BTXA to improve the ability of patients to walk independently, with the high-dose/low-concentration combination providing the best effect. Onset and duration of the ameliorating effects of BTXA were 4–7 days and 12 weeks, respectively. Thus, BTXA effectively treated foot spasms after stroke at an optimal dose of 400 U and concentration of 50 U/mL.

  9. Lack of Effect of Sodium Benzoate at Reported Clinical Therapeutic Concentration on d-Alanine Metabolism in Dogs.

    Science.gov (United States)

    Popiolek, Michael; Tierney, Brendan; Steyn, Stefanus J; DeVivo, Michael

    2018-06-19

    Cognitive decline and psychosis have been hypothesized to be mediated by N-methyl-d-aspartate receptor (NMDAR) hypofunction. Consistent with this hypothesis, chronic treatment with d-alanine, a coagonist at the glycine site of the NMDAR, leads to an improvement of positive and cognitive symptoms in schizophrenic patients. d-alanine is oxidized by d-amino acid oxidase (DAAO); thus, an inhibitor of DAAO would be expected to enhance d-alanine levels and likewise lead to desirable clinical outcomes. Sodium benzoate, on the basis of d-amino acid inhibition, was observed to display beneficial clinical effects in schizophrenic and Alzheimer's patients. However, in the clinical pilot studies using sodium benzoate, d-amino acids were not quantified to verify that sodium benzoate's efficacy was mediated through DAAO inhibition. In this study, d-alanine content was monitored in cerebral spinal fluid (CSF) of dogs treated with daily injections of d-alanine (30 mg/kg) alone and in combination with sodium benzoate (30 mg/kg) for seven consecutive days. We reasoned that the cerebral spinal fluid d-alanine quantity is reflective of the brain d-alanine levels and it would increase as a consequence of DAAO inhibition with sodium benzoate. We found that d-alanine treatment lead to maximal concentration of 7.51 μM CSF d-alanine level; however, coadministration of sodium benzoate and d-alanine did not change CSF d-alanine level beyond that of d-alanine treatment alone. As a consequence, we conclude that clinical efficacy associated with chronic administration of sodium benzoate in schizophrenic and Alzheimer's patients is likely not mediated through inhibition of DAAO.

  10. Tenofovir alafenamide (TAF) does not deplete mitochondrial DNA in human T-cell lines at intracellular concentrations exceeding clinically relevant drug exposures.

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    Stray, Kirsten M; Park, Yeojin; Babusis, Darius; Callebaut, Christian; Cihlar, Tomas; Ray, Adrian S; Perron, Michel

    2017-04-01

    HIV-infected patients treated with certain nucleoside reverse transcriptase inhibitors (NRTIs) have experienced adverse effects due to drug-related mitochondrial toxicity. Tenofovir alafenamide (TAF) is a novel prodrug of the NRTI tenofovir (TFV) with an improved safety profile compared to tenofovir disoproxil fumarate (TDF). Prior in vitro studies have demonstrated that the parent nucleotide TFV has no significant effects on mtDNA synthesis. This study investigated whether clinically relevant TAF and TDF exposures affect mtDNA content in human lymphocytes. First, activated or resting peripheral blood mononuclear cells (PBMCs), as well as MT-2 and Jurkat T-cell lines, were continuously treated with ddC for 10 days to establish their susceptibility to mtDNA depletion. PBMCs had low sensitivity to NRTI-mediated mtDNA depletion in vitro. In contrast, ddC treatment of rapidly dividing MT-2 and Jurkat cells resulted in a dose-dependent decrease in mtDNA. Therefore, these two T-cell lines were selected for evaluating TAF and TDF treatment effects. MT-2 and Jurkat cells were pulse-treated with TAF or TDF every 24 h for 10 days to mimic pharmacologically relevant drug exposures. Pulse treatment of cells with 3.3 μM TAF or 1.1 μM TDF for 10 days resulted in 2- to 7-fold greater steady-state intracellular TFV-diphosphate (TFV-DP) levels than those observed clinically in TAF- or TDF-treated patients. At these concentrations, no significant TAF- (106.7% and 84.1% of control; p = 0.77 and 0.12 for MT-2 and Jurkat, respectively) or TDF- (100.6% and 91.0% of control; p = 0.91 and 0.37, respectively) associated reduction in mtDNA content was observed compared with untreated control cells. This study demonstrates that, despite delivering higher intracellular levels of TFV-DP than TDF, TAF does not inhibit mtDNA synthesis in vitro at concentrations exceeding the clinically relevant intracellular drug exposures. Thus, TAF has a low potential for mitochondrial toxicity in

  11. Development, validation, and application of a fast and simple GC-MS method for determination of some therapeutic drugs relevant in emergency toxicology.

    Science.gov (United States)

    Meyer, Markus R; Welter, Jessica; Weber, Armin A; Maurer, Hans H

    2011-10-01

    To date, immunoassays are commercially available for quantification of valproic acid, salicylic acid, paracetamol, phenobarbital, phenytoin, and primidone. As they are no longer available, a fast, simple, and cost-effective quantitative gas chromatography-mass spectrometry (GC-MS) method was developed and fully validated for these drugs. After simple and fast liquid-liquid extraction, the samples were analyzed by GC-MS using the selected ion monitoring mode. The method was validated including the parameters selectivity, calibration model, precision, accuracy, and extraction efficiency. The above-mentioned analytes were separated within 8.5 minutes and sensitively detected. No interfering peaks were observed in blank samples from 8 different sources. The linearity ranges were 20-200 mg/L for valproic acid, 100-1200 mg/L for salicylic acid, 10-200 mg/L for paracetamol, 10-200 mg/L for phenobarbital, 4-20 mg/L for primidone, and 2.5-30 mg/L for phenytoin. Generally accepted criteria for accuracy and precision were fulfilled for all analytes using 6-point calibration. Even 1-point calibration was applicable for all analytes. The assay was successfully applied to analysis of real plasma samples and proficiency testing material. The assay described allowed fast and reliable determination of analytes relevant in the diagnosis of poisonings. Furthermore, time- and cost-saving 1-point calibration was shown to be suitable for daily routine work, especially in emergency cases.

  12. Is photodynamic therapy a relevant therapeutic option in refractory benign familial pemphigus (Hailey-Hailey disease)? A series of eight patients.

    Science.gov (United States)

    Alsahli, Maha; Debu, Anca; Girard, Celine; Bessis, Didier; Du Thanh, Aurélie; Guillot, Bernard; Dereure, Olivier

    2017-11-01

    Treatment of benign familial pemphigus or Hailey-Hailey disease (HHD), a rare inherited condition associated with a significant impairment of quality of life, is often challenging and disappointing with frequent relapses and infectious complications. Topical photodynamic therapy (PDT) may offer new perspectives in this difficult setting. Eight patients with long-lasting HHD lesions refractory to multiple treatments were treated on at least one involved site with PDT using methyl-amino levulinate with a standardized protocol of three sessions of irradiation separated by 3-week intervals. A complete or partial clearing was achieved in all treated areas, and the result was satisfactorily maintained in all cases after a follow-up period ranging from 3 to 36 months. Results were of higher quality in non-inguinal areas. Tolerance was overall acceptable with local pain during and shortly after irradiation being the main limiting factor. Our series, although limited in size, emphasizes the interest of PDT in this difficult condition even though results may be incomplete. Treatment-related pain can be adequately managed by prior analgesics, cooling with sprayed water and local tumescent anesthesia. Overall, PDT appears as a relevant option in refractory HHD management with a favorable benefit/risk ratio.

  13. Comparison of cell-based and non-cell-based assay platforms for the detection of clinically relevant anti-drug neutralizing antibodies for immunogenicity assessment of therapeutic proteins.

    Science.gov (United States)

    Hu, Jenny; Wala, Iwona; Han, Hong; Nagatani, Janice; Barger, Troy; Civoli, Francesca; Kaliyaperumal, Arunan; Zhuang, Yao; Gupta, Shalini

    2015-04-01

    Anti-drug neutralizing antibodies (NAbs) formed due to unwanted immunogenicity of a therapeutic protein point towards a mature immune response. NAb detection is important in interpreting the therapeutic's efficacy and safety in vivo. In vitro cell-based NAb assays provide a physiological system for NAb detection, however are complex assays. Non-cell-based competitive ligand binding (CLB) approaches are also employed for NAb detection. Instead of cells, CLB assays use soluble receptor and conjugated reagents and are easier to perform, however have reduced physiological relevance. The aim of this study was to compare the performance of CLB assays to established cell-based assays to determine the former's ability to detect clinically relevant NAbs towards therapeutics that (i) acted as an agonist or (ii) acted as antagonists by binding to a target receptor. We performed a head-to-head comparison of the performance of cell-based and CLB NAb assays for erythropoietin (EPO) and two anti-receptor monoclonal antibodies (AMG-X and AMG 317). Clinically relevant NAb-positive samples identified previously by a cell-based assay were assessed in the corresponding CLB format(s). A panel of 12 engineered fully human anti-EPO monoclonal antibodies (MAbs) was tested in both EPO NAb assay formats. Our results showed that the CLB format was (i) capable of detecting human anti-EPO MAbs of differing neutralizing capabilities and affinities and (ii) provided similar results as the cell-based assay for detecting NAbs in patient samples. The cell-based and CLB assays also behaved comparably in detecting NAbs in clinical samples for AMG-X. In the case of anti-AMG 317 NAbs, the CLB format failed to detect NAbs in more than 50% of the tested samples. We conclude that assay sensitivity, drug tolerance and the selected assay matrix played an important role in the inability of AMG 317 CLB assays to detect clinically relevant NAbs. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. p,p'-DDE Induces Gonadal Intersex in Japanese Medaka (Oryzias latipes) at Environmentally Relevant Concentrations: Comparison with o,p'-DDT.

    Science.gov (United States)

    Sun, Jianxian; Wang, Chen; Peng, Hui; Zheng, Guomao; Zhang, Shiyi; Hu, Jianying

    2016-01-05

    Previous studies have reported high body burdens of dichlorodiphenyltrichloroethane (DDT) and its metabolites in wild fishes worldwide. This study evaluated the adverse effects of 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) and o,p'-DDT on gonadal development and reproduction by exposing transgenic Japanese medaka (Oryzias latipes) from hatch for 100 days. While both p,p'-DDE and o,p'-DDT induced intersex in male medaka, the lowest observable effective concentration (LOEC) of o,p'-DDT was 57.7 ng/g ww, about 5-fold lower than that (272 ng/g ww) of p,p'-DDE. Since LOECs of both chemicals were comparable to the body concentrations in wild fish, DDT contamination would likely contribute to the occurrence of intersex observed in wild fish. Exposure to o,p'-DDT resulted in much higher expression of vitellogenin in liver of males than p,p'-DDE, accordant with the higher potency of o,p'-DDT than p,p'-DDE to induce intersex. This phenomenon could be partly explained by the significantly elevated levels of 17β-estradiol in plasma of males exposed to o,p'-DDT, in addition to its estrogenic activity via the estrogen receptor. Significantly lower fertilization (p = 0.006) and hatchability (p = 0.019) were observed in the 13 intersex males. This study for the first time demonstrated the induction of intersex and reproductive effects of p,p'-DDE and o,p'-DDT at environmentally relevant concentrations.

  15. Beta-defensin-2 protein is a serum biomarker for disease activity in psoriasis and reaches biologically relevant concentrations in lesional skin.

    Directory of Open Access Journals (Sweden)

    Patrick A M Jansen

    Full Text Available BACKGROUND: Previous studies have extensively documented antimicrobial and chemotactic activities of beta-defensins. Human beta-defensin-2 (hBD-2 is strongly expressed in lesional psoriatic epidermis, and recently we have shown that high beta-defensin genomic copy number is associated with psoriasis susceptibility. It is not known, however, if biologically and pathophysiologically relevant concentrations of hBD-2 protein are present in vivo, which could support an antimicrobial and proinflammatory role of beta-defensins in lesional psoriatic epidermis. METHODOLOGY/PRINCIPAL FINDINGS: We found that systemic levels of hBD-2 showed a weak but significant correlation with beta defensin copy number in healthy controls but not in psoriasis patients with active disease. In psoriasis patients but not in atopic dermatitis patients, we found high systemic hBD-2 levels that strongly correlated with disease activity as assessed by the PASI score. Our findings suggest that systemic levels in psoriasis are largely determined by secretion from involved skin and not by genomic copy number. Modelling of the in vivo epidermal hBD-2 concentration based on the secretion rate in a reconstructed skin model for psoriatic epidermis provides evidence that epidermal hBD-2 levels in vivo are probably well above the concentrations required for in vitro antimicrobial and chemokine-like effects. CONCLUSIONS/SIGNIFICANCE: Serum hBD-2 appears to be a useful surrogate marker for disease activity in psoriasis. The discrepancy between hBD-2 levels in psoriasis and atopic dermatitis could explain the well known differences in infection rate between these two diseases.

  16. The intake of water containing a mix of pollutants at environmentally relevant concentrations leads to defensive response deficit in male C57Bl/6J mice.

    Science.gov (United States)

    de Souza, Joyce Moreira; Rabelo, Letícia Martins; de Faria, Denise Braga Gomes; Guimarães, Abraão Tiago Batista; da Silva, Wellington Alves Mizael; Rocha, Thiago Lopes; Estrela, Fernanda Neves; Chagas, Thales Quintão; de Oliveira Mendes, Bruna; Malafaia, Guilherme

    2018-07-01

    Previous studies have individually confirmed the toxic effects from different pollutants on mammals. However, effects resulting from the exposure of these animals to multi-pollutant mixes have not been studied so far. Thus, the aim of the current study is to assess the effect from the chronic exposure (105days) of C57Bl/6J mice to a mix of pollutants on their response to potential predators. In order to do so, the following groups were formed: "control", "Mix 1× [compounds from 15 pollutants identified in surface waters at environmentally relevant concentration (ERC)]", "Mix 10×" and "Mix 25×" (concentrations 10 and 25 times higher than the ERC). From the 100th experimental day on, the animals were subjected to tests in order to investigate whether they showed locomotor, visual, olfactory and auditory changes, since these abilities are essential to their anti-predatory behavior. Next, the animals' behavior towards potential predators (Felis catus and Pantherophis guttatus) was assessed. The herein collected data did not show defensive response from any of the experimental groups to the predatory stimulus provided by P. guttatus. However, the control animals, only, presented anti-predatory behavior when F. catus was introduced in the apparatus, fact that suggests defensive response deficit resulting from the treatments. Thus, the current study is pioneer in showing that the chronic intake of water containing a mix of pollutants (even at low concentrations) leads to behavioral disorders able to affect the survival and population dynamics of mammalian species at ecological level. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Clinically Relevant Plasma Concentrations of Colistin in Combination with Imipenem Enhance Pharmacodynamic Activity against Multidrug-Resistant Pseudomonas aeruginosa at Multiple Inocula▿†

    Science.gov (United States)

    Bergen, Phillip J.; Forrest, Alan; Bulitta, Jürgen B.; Tsuji, Brian T.; Sidjabat, Hanna E.; Paterson, David L.; Li, Jian; Nation, Roger L.

    2011-01-01

    The use of combination antibiotic therapy may be beneficial against rapidly emerging resistance in Pseudomonas aeruginosa. The aim of this study was to systematically investigate in vitro bacterial killing and resistance emergence with colistin alone and in combination with imipenem against multidrug-resistant (MDR) P. aeruginosa. Time-kill studies were conducted over 48 h using 5 clinical isolates and ATCC 27853 at two inocula (∼106 and ∼108 CFU/ml); MDR, non-MDR, and colistin-heteroresistant and -resistant strains were included. Nine colistin-imipenem combinations were investigated. Microbiological response was examined by log changes at 6, 24, and 48 h. Colistin combined with imipenem at clinically relevant concentrations increased the levels of killing of MDR and colistin-heteroresistant isolates at both inocula. Substantial improvements in activity with combinations were observed across 48 h with all colistin concentrations at the low inoculum and with colistin at 4× and 16× MIC (or 4 and 32 mg/liter) at the high inoculum. Combinations were additive or synergistic against imipenem-resistant isolates (MICs, 16 and 32 mg/liter) at the 106-CFU inoculum in 9, 11, and 12 of 18 cases (i.e., 9 combinations across 2 isolates) at 6, 24, and 48 h, respectively, and against the same isolates at the 108-CFU inoculum in 11, 7, and 8 cases, respectively. Against a colistin-resistant strain (MIC, 128 mg/liter), combinations were additive or synergistic in 9 and 8 of 9 cases at 24 h at the 106- and 108-CFU inocula, respectively, and in 5 and 7 cases at 48 h. This systematic study provides important information for optimization of colistin-imipenem combinations targeting both colistin-susceptible and colistin-resistant subpopulations. PMID:21876058

  18. Nonproteinogenic D-amino acids at millimolar concentrations are a toxin for anaerobic microorganisms relevant to early Earth and other anoxic planets.

    Science.gov (United States)

    Nixon, Sophie L; Cockell, Charles S

    2015-03-01

    The delivery of extraterrestrial organics to early Earth provided a potentially important source of carbon and energy for microbial life. Optically active organic compounds of extraterrestrial origin exist in racemic form, yet life on Earth has almost exclusively selected for L- over D-enantiomers of amino acids. Although D-enantiomers of proteinogenic amino acids are known to inhibit aerobic microorganisms, the role of concentrated nonproteinogenic meteoritic D-amino acids on anaerobic metabolisms relevant to early Earth and other anoxic planets such as Mars is unknown. Here, we test the inhibitory effect of D-enantiomers of two nonproteinogenic amino acids common to carbonaceous chondrites, norvaline and α-aminobutyric acid, on microbial iron reduction. Three pure strains (Geobacter bemidjiensis, Geobacter metallireducens, Geopsychrobacter electrodiphilus) and an iron-reducing enrichment culture were grown in the presence of 10 mM D-enantiomers of both amino acids. Further tests were conducted to assess the inhibitory effect of these D-amino acids at 1 and 0.1 mM. The presence of 10 mM D-norvaline and D-α-aminobutyric acid inhibited microbial iron reduction by all pure strains and the enrichment. G. bemidjiensis was not inhibited by either amino acid at 0.1 mM, but D-α-aminobutyric acid still inhibited at 1 mM. Calculations using published meteorite accumulation rates to the martian surface indicate D-α-aminobutyric acid may have reached inhibitory concentrations in little over 1000 years during peak infall. These data show that, on a young anoxic planet, the use of one enantiomer over another may render the nonbiological enantiomer an environmental toxin. Processes that generate racemic amino acids in the environment, such as meteoritic infall or impact synthesis, would have been toxic processes and could have been a selection pressure for the evolution of early racemases.

  19. Therapeutic Nanodevices

    Science.gov (United States)

    Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

    Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

  20. Effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs on the production of reactive oxygen species by activated rat neutrophils

    Directory of Open Access Journals (Sweden)

    Paino I.M.M.

    2005-01-01

    Full Text Available The release of reactive oxygen specie (ROS by activated neutrophil is involved in both the antimicrobial and deleterious effects in chronic inflammation. The objective of the present investigation was to determine the effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs (NSAIDs on the production of ROS by stimulated rat neutrophils. Diclofenac (3.6 µM, indomethacin (12 µM, naproxen (160 µM, piroxicam (13 µM, and tenoxicam (30 µM were incubated at 37ºC in PBS (10 mM, pH 7.4, for 30 min with rat neutrophils (1 x 10(6 cells/ml stimulated by phorbol-12-myristate-13-acetate (100 nM. The ROS production was measured by luminol and lucigenin-dependent chemiluminescence. Except for naproxen, NSAIDs reduced ROS production: 58 ± 2% diclofenac, 90 ± 2% indomethacin, 33 ± 3% piroxicam, and 45 ± 6% tenoxicam (N = 6. For the lucigenin assay, naproxen, piroxicam and tenoxicam were ineffective. For indomethacin the inhibition was 52 ± 5% and diclofenac showed amplification in the light emission of 181 ± 60% (N = 6. Using the myeloperoxidase (MPO/H2O2/luminol system, the effects of NSAIDs on MPO activity were also screened. We found that NSAIDs inhibited both the peroxidation and chlorinating activity of MPO as follows: diclofenac (36 ± 10, 45 ± 3%, indomethacin (97 ± 2, 100 ± 1%, naproxen (56 ± 8, 76 ± 3%, piroxicam (77 ± 5, 99 ± 1%, and tenoxicam (90 ± 2, 100 ± 1%, respectively (N = 3. These results show that therapeutic levels of NSAIDs are able to suppress the oxygen-dependent antimicrobial or oxidative functions of neutrophils by inhibiting the generation of hypochlorous acid.

  1. The mixture of "ecstasy" and its metabolites impairs mitochondrial fusion/fission equilibrium and trafficking in hippocampal neurons, at in vivo relevant concentrations.

    Science.gov (United States)

    Barbosa, Daniel José; Serrat, Romàn; Mirra, Serena; Quevedo, Martí; de Barreda, Elena Goméz; Àvila, Jesús; Ferreira, Luísa Maria; Branco, Paula Sério; Fernandes, Eduarda; Lourdes Bastos, Maria de; Capela, João Paulo; Soriano, Eduardo; Carvalho, Félix

    2014-06-01

    3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a potentially neurotoxic recreational drug of abuse. Though the mechanisms involved are still not completely understood, formation of reactive metabolites and mitochondrial dysfunction contribute to MDMA-related neurotoxicity. Neuronal mitochondrial trafficking, and their targeting to synapses, is essential for proper neuronal function and survival, rendering neurons particularly vulnerable to mitochondrial dysfunction. Indeed, MDMA-associated disruption of Ca(2+) homeostasis and ATP depletion have been described in neurons, thus suggesting possible MDMA interference on mitochondrial dynamics. In this study, we performed real-time functional experiments of mitochondrial trafficking to explore the role of in situ mitochondrial dysfunction in MDMA's neurotoxic actions. We show that the mixture of MDMA and six of its major in vivo metabolites, each compound at 10μM, impaired mitochondrial trafficking and increased the fragmentation of axonal mitochondria in cultured hippocampal neurons. Furthermore, the overexpression of mitofusin 2 (Mfn2) or dynamin-related protein 1 (Drp1) K38A constructs almost completely rescued the trafficking deficits caused by this mixture. Finally, in hippocampal neurons overexpressing a Mfn2 mutant, Mfn2 R94Q, with impaired fusion and transport properties, it was confirmed that a dysregulation of mitochondrial fission/fusion events greatly contributed to the reported trafficking phenotype. In conclusion, our study demonstrated, for the first time, that the mixture of MDMA and its metabolites, at concentrations relevant to the in vivo scenario, impaired mitochondrial trafficking and increased mitochondrial fragmentation in hippocampal neurons, thus providing a new insight in the context of "ecstasy"-induced neuronal injury.

  2. Environmentally relevant concentrations of di(2-ethylhexyl)phthalate exposure alter larval growth and locomotion in medaka fish via multiple pathways.

    Science.gov (United States)

    Yang, Wen-Kai; Chiang, Li-Fen; Tan, Shi-Wei; Chen, Pei-Jen

    2018-06-01

    Di(2-ethylhexyl)phthalate (DEHP) is a commonly used plasticizer, with evidence of ubiquitous human exposure and widespread occurrence in the aquatic environment. It is an emerging environmental pollutant with regulatory priority; however, most studies have focused on the toxicity of DEHP related to endocrine disruption and reproduction in mammals. The ecotoxicological impact of phthalates (e.g., DEHP) on early life stages of fish under environmentally relevant concentrations of chronic exposure remains unclear. In this study, 7-day post-hatching fry of medaka fish (Oryzias latipes) underwent 21-day continuous exposure to DEHP solutions at 20, 100 and 200 μg/L to assess the effects on fish development and locomotion and related toxic mechanisms. Larval mortality was low with DEHP (20-200 μg/L) within 21 days, but such exposure significantly reduced fish body weight and length and altered swimming behavior. At 21 days, DEHP exposure resulted in specific patterns of larval locomotion (e.g., increased maximum velocity and absolute turn angle) and dose-dependently increased the mRNA expression of acetylcholinesterase (ache) but did not alter AChE activity. Transcriptional expression of antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase and peroxisome proliferation-activated receptor and retinoid X receptor genes was significantly suppressed with 21-day DEHP exposure (20-200 μg/L), with marginal alteration in reactive oxygen species levels and antioxidant activities within the dosing period. As well, DEHP altered the mRNA expression of p53-regulated apoptosis pathways, such as upregulated p53, p21 and bcl-2 and downregulated caspase-3 expression, with increased enzymatic activity of caspase-3 in larvae. Our results suggest that toxic mechanisms of waterborne DEHP altered fish growth and locomotion likely via a combined effect of oxidative stress, neurotoxicity and apoptosis pathways. Copyright © 2018

  3. Clinical relevance of the discrepancy in phenylalanine concentrations analyzed using tandem mass spectrometry compared with ion-exchange chromatography in phenylketonuria

    Directory of Open Access Journals (Sweden)

    Bridget M. Stroup

    2016-03-01

    Conclusion: Use of DBS analyzed using MS/MS to monitor blood phe concentrations in individuals with PKU yields significantly lower phe levels compared to plasma phe levels analyzed using IEC. Optimization of current testing methodologies for measuring phe in DBS, along with patient education regarding the appropriate technique for spotting blood on filter paper is needed to improve the accuracy of using DBS to measure phe concentrations in PKU management.

  4. Analysis of Blood Concentrations of Zinc, Germanium, and Lead and Relevant Environmental Factors in a Population Sample from Shandong Province, China

    Directory of Open Access Journals (Sweden)

    Long Li

    2017-02-01

    Full Text Available Trace elements, including zinc (Zn and germanium (Ge, are essential for health; deficiency or excess levels of trace elements results is harmful. As a result of industrial and agricultural production, Pb widely exists in people’s living environment. It is absorbed mainly through the respiratory and digestive tracts, producing systemic harm. Reference values for a normal, healthy population are necessary for health assessment, prevention and treatment of related diseases, and evaluation of occupational exposures. Reference ranges for the Chinese population have not been established. From March 2009 to February 2010; we collected data and blood samples (n = 1302 from residents aged 6–60 years living in Shandong Province, China. We measured blood concentrations of Zn, Ge, and Pb using inductively coupled plasma mass spectrometry to determine reference ranges. Results were stratified by factors likely to affect the concentrations of these trace elements: sex, use of cosmetics or hair dye, age, alcohol intake, smoking habits, and consumption of fried food. The overall geometric mean (GM concentrations (95% confidence interval were 3.14 (3.08–3.20 mg/L for Zn, 19.9 (19.3–20.6 μg/L for Ge, and 24.1 (23.2–25.1 μg/L for Pb. Blood Zn concentrations were higher in women than in men (p < 0.001, while the opposite was found for Pb (p < 0.001 and sex did not influence Ge (p = 0.095. Alcohol use was associated with higher blood concentrations of Zn (p = 0.002, Ge (p = 0.002, and Pb (p = 0.001. The GM concentration of Zn was highest in 20–30-year-olds (p < 0.001, while Pb concentrations were highest in 12–16-year-olds (p < 0.001. Use of hair dye was associated with lower blood concentrations of Ge (p < 0.05. GM blood concentrations of Pb differed significantly between those who consumed fried foods 1–2 times/month (18.7 μg/L, 1–2 times/week (20.9 μg/L, and every day (28.5 μg/L; p < 0.001. Blood Pb concentrations were higher in subjects

  5. Environmentally relevant pyrethroid mixtures: A study on the correlation of blood and brain concentrations of a mixture of pyrethroid insecticides to motor activity in the rat.

    Science.gov (United States)

    Hughes, Michael F; Ross, David G; Starr, James M; Scollon, Edward J; Wolansky, Marcelo J; Crofton, Kevin M; DeVito, Michael J

    2016-06-01

    Human exposure to multiple pyrethroid insecticides may occur because of their broad use on crops and for residential pest control. To address the potential health risk from co-exposure to pyrethroids, it is important to understand their disposition and toxicity in target organs such as the brain, and surrogates such as the blood when administered as a mixture. The objective of this study was to assess the correlation between blood and brain concentrations of pyrethroids and neurobehavioral effects in the rat following an acute oral administration of the pyrethroids as a mixture. Male Long-Evans rats were administered a mixture of β-cyfluthrin, cypermethrin, deltamethrin, esfenvalerate and cis- and trans-permethrin in corn oil at seven dose levels. The pyrethroid with the highest percentage in the dosing solution was trans-permethrin (31% of total mixture dose) while deltamethrin and esfenvalerate had the lowest percentage (3%). Motor activity of the rats was then monitored for 1h. At 3.5h post-dosing, the animals were euthanized and blood and brain were collected. These tissues were extracted and analyzed for parent pyrethroid using HPLC-tandem mass spectrometry. Cypermethrin and cis-permethrin were the predominate pyrethroids detected in blood and brain, respectively, at all dosage levels. The relationship of total pyrethroid concentration between blood and brain was linear (r=0.93). The pyrethroids with the lowest fraction in blood were trans-permethrin and β-cyfluthrin and in brain were deltamethrin and esfenvalerate. The relationship between motor activity of the treated rats and summed pyrethroid blood and brain concentration was described using a sigmoidal Emax model with the Effective Concentration50 being more sensitive for brain than blood. The data suggests summed pyrethroid rat blood concentration could be used as a surrogate for brain concentration as an aid to study the neurotoxic effects of pyrethroids administered as a mixture under the conditions

  6. Gas-phase naphthalene concentration data recovery in ambient air and its relevance as a tracer of sources of volatile organic compounds

    Science.gov (United States)

    Uria-Tellaetxe, Iratxe; Navazo, Marino; de Blas, Maite; Durana, Nieves; Alonso, Lucio; Iza, Jon

    2016-04-01

    Despite the toxicity of naphthalene and the fact that it is a precursor of atmospheric photooxidants and secondary aerosol, studies on ambient gas-phase naphthalene are generally scarce. Moreover, as far as we are concerned, this is the first published one using long-term hourly ambient gas-phase naphthalene concentrations. In this work, it has been also demonstrated the usefulness of ambient gas-phase naphthalene to identify major sources of volatile organic compounds (VOC) in complex scenarios. Initially, in order to identify main benzene emission sources, hourly ambient measurements of 60 VOC were taken during a complete year together with meteorological data in an urban/industrial area. Later, due to the observed co-linearity of some of the emissions, a procedure was developed to recover naphthalene concentration data from recorded chromatograms to use it as a tracer of the combustion and distillation of petroleum products. The characteristic retention time of this compound was determined comparing previous GC-MS and GC-FID simultaneous analysis by means of relative retention times, and its concentration was calculated by using relative response factors. The obtained naphthalene concentrations correlated fairly well with ethene (r = 0.86) and benzene (r = 0.92). Besides, the analysis of daily time series showed that these compounds followed a similar pattern, very different from that of other VOC, with minimum concentrations at day-time. This, together with the results from the assessment of the meteorological dependence pointed out a coke oven as the major naphthalene and benzene emitting sources in the study area.

  7. An alkaline comet assay study on the antimalarial drug atovaquone in human peripheral blood lymphocytes: a study based on clinically relevant concentrations.

    Science.gov (United States)

    Dinter, Domagoj; Gajski, Goran; Garaj-Vrhovac, Vera

    2013-01-01

    Atovaquone, a hydroxynaphthoquinone, is an anti-parasite drug, selectively targeting the mitochondrial respiratory chain of malaria parasite. It is used for both the treatment and prevention of malaria, usually in a fixed combination with proguanil. Although atovaquone has not often been associated with severe adverse reactions in the recommended dosages and has a relatively favorable side effect profile, the present study was undertaken to evaluate its cytogenotoxic potential towards human peripheral blood lymphocytes. Two different concentrations of atovaquone found in plasma when used in fixed-dose combination with proguanile hydrochloride were used with and without S9 metabolic activation: 2950 ng ml(-1) used for prophylactic treatment and 11 800 ng ml(-1) used in treatment of malaria. The results showed that lymphocyte viability was not affected after the treatment, suggesting that atovaquone was not cytotoxic in the given concentrations. With the alkaline comet assay we demonstrated that in human peripheral blood lymphocytes no significant changes in comet parameters occurred after the treatment. There were no differences in tested parameters with the addition of S9 metabolic activation, indicating that atovaquone either has no metabolite or it is not toxic in the given concentrations. Since no effects were observed after the treatment, it is to be concluded that atovaquone is safe from the aspect of genototoxicity in the recommended dosages. Copyright © 2011 John Wiley & Sons, Ltd.

  8. Concentrations of polybrominated diphenyl ethers (PBDEs) in central air-conditioner filter dust and relevance of non-dietary exposure in occupational indoor environments in Greece

    International Nuclear Information System (INIS)

    Besis, Athanasios; Katsoyiannis, Athanasios; Botsaropoulou, Elisavet; Samara, Constantini

    2014-01-01

    Polybrominated Diphenyl Ethers (PBDEs) are ubiquitous in the indoor environment owing to their use in consumer products and various studies around the world have found higher concentrations indoors than outdoors. Central air conditioner (A/C) systems have been widely used in many workplaces, therefore, studying of PBDEs in central A/C filter dust is useful to better understand the occurrences and health implications of PBDEs in indoor environments. The present study examined the occurrence of PBDEs in central A/C filter dust collected from various workplaces (n = 20) in Thessaloniki, Greece. The sum concentrations of 21 target congeners (∑ 21 PBDE) in A/C dust ranged between 84 and 4062 ng g −1 with a median value of 1092 ng g −1 , while BDE-209 was found to be the most abundant BDE congener. The daily intake via dust ingestion of PBDEs estimated for the employees of the occupational settings ranged from 3 to 45 ng day −1 (median 12 ng day −1 ). - Highlights: • PBDEs were investigated in dust of A/C filters in occupational settings in Thessaloniki, Greece. • BDE-209 was found to be the most abundant BDE congener. • High levels of PBDEs were found in a newspaper building, internet cafes and electronic shops. • PBDEs were attributable to the extensive presence and/or usage of electronic devices. • Exposure of employees to PBDEs via indoor dust ingestion was estimated at 12 ng day −1 . - PBDEs were for the first time measured in dust from central A/C filters in workplaces of Greece and their concentrations were used to estimate the non-dietary human exposure

  9. At clinically relevant concentrations the anaesthetic/amnesic thiopental but not the anticonvulsant phenobarbital interferes with hippocampal sharp wave-ripple complexes

    Science.gov (United States)

    Papatheodoropoulos, Costas; Sotiriou, Evangelos; Kotzadimitriou, Dimitrios; Drimala, Panagiota

    2007-01-01

    Background Many sedative agents, including anesthetics, produce explicit memory impairment by largely unknown mechanisms. Sharp-wave ripple (SPW-R) complexes are network activity thought to represent the neuronal substrate for information transfer from the hippocampal to neocortical circuits, contributing to the explicit memory consolidation. In this study we examined and compared the actions of two barbiturates with distinct amnesic actions, the general anesthetic thiopental and the anticonvulsant phenobarbital, on in vitro SPW-R activity. Results Using an in vitro model of SPW-R activity we found that thiopental (50–200 μM) significantly and concentration-dependently reduced the incidence of SPW-R events (it increased the inter-event period by 70–430 %). At the concentration of 25 μM, which clinically produces mild sedation and explicit memory impairment, thiopental significantly reduced the quantity of ripple oscillation (it reduced the number of ripples and the duration of ripple episodes by 20 ± 5%, n = 12, P Phenobarbital significantly accelerated SPWs at 50 and 100 μM whereas it reduced their rate at 200 and 400 μM. Furthermore, it significantly prolonged SPWs, reduced their synchrony and reduced the quantity of ripples only at the clinically very high concentration of 400 μM, reported to affect memory. Conclusion We hypothesize that thiopental, by interfering with SPW-R activity, through enhancement of the GABAA receptor-mediated transmission, affects memory processes which involve hippocampal circuit activation. The quantity but not the frequency of ripple oscillation was affected by the drug. PMID:17672909

  10. Concentrations of polybrominated diphenyl ethers (PBDEs) in central air-conditioner filter dust and relevance of non-dietary exposure in occupational indoor environments in Greece.

    Science.gov (United States)

    Besis, Athanasios; Katsoyiannis, Athanasios; Botsaropoulou, Elisavet; Samara, Constantini

    2014-05-01

    Polybrominated Diphenyl Ethers (PBDEs) are ubiquitous in the indoor environment owing to their use in consumer products and various studies around the world have found higher concentrations indoors than outdoors. Central air conditioner (A/C) systems have been widely used in many workplaces, therefore, studying of PBDEs in central A/C filter dust is useful to better understand the occurrences and health implications of PBDEs in indoor environments. The present study examined the occurrence of PBDEs in central A/C filter dust collected from various workplaces (n = 20) in Thessaloniki, Greece. The sum concentrations of 21 target congeners (∑21PBDE) in A/C dust ranged between 84 and 4062 ng g(-1) with a median value of 1092 ng g(-1), while BDE-209 was found to be the most abundant BDE congener. The daily intake via dust ingestion of PBDEs estimated for the employees of the occupational settings ranged from 3 to 45 ng day(-1) (median 12 ng day(-1)). Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Telecommunication Support System Using Keywords and Their Relevant Information in Videoconferencing — Presentation Method for Keeping Audience's Concentration at Distance Lectures

    Science.gov (United States)

    Asai, Kikuo; Kondo, Kimio; Kobayashi, Hideaki; Saito, Fumihiko

    We developed a prototype system to support telecommunication by using keywords selected by the speaker in a videoconference. In the traditional presentation style, a speaker talks and uses audiovisual materials, and the audience at remote sites looks at these materials. Unfortunately, the audience often loses concentration and attention during the talk. To overcome this problem, we investigate a keyword presentation style, in which the speaker holds keyword cards that enable the audience to see additional information. Although keyword captions were originally intended for use in video materials for learning foreign languages, they can also be used to improve the quality of distance lectures in videoconferences. Our prototype system recognizes printed keywords in a video image at a server, and transfers the data to clients as multimedia functions such as language translation, three-dimensional (3D) model visualization, and audio reproduction. The additional information is collocated to the keyword cards in the display window, thus forming a spatial relationship between them. We conducted an experiment to investigate the properties of the keyword presentation style for an audience. The results suggest the potential of the keyword presentation style for improving the audience's concentration and attention in distance lectures by providing an environment that facilitates eye contact during videoconferencing.

  12. At clinically relevant concentrations the anaesthetic/amnesic thiopental but not the anticonvulsant phenobarbital interferes with hippocampal sharp wave-ripple complexes

    Directory of Open Access Journals (Sweden)

    Sotiriou Evangelos

    2007-07-01

    Full Text Available Abstract Background Many sedative agents, including anesthetics, produce explicit memory impairment by largely unknown mechanisms. Sharp-wave ripple (SPW-R complexes are network activity thought to represent the neuronal substrate for information transfer from the hippocampal to neocortical circuits, contributing to the explicit memory consolidation. In this study we examined and compared the actions of two barbiturates with distinct amnesic actions, the general anesthetic thiopental and the anticonvulsant phenobarbital, on in vitro SPW-R activity. Results Using an in vitro model of SPW-R activity we found that thiopental (50–200 μM significantly and concentration-dependently reduced the incidence of SPW-R events (it increased the inter-event period by 70–430 %. At the concentration of 25 μM, which clinically produces mild sedation and explicit memory impairment, thiopental significantly reduced the quantity of ripple oscillation (it reduced the number of ripples and the duration of ripple episodes by 20 ± 5%, n = 12, P P P Conclusion We hypothesize that thiopental, by interfering with SPW-R activity, through enhancement of the GABAA receptor-mediated transmission, affects memory processes which involve hippocampal circuit activation. The quantity but not the frequency of ripple oscillation was affected by the drug.

  13. Perfluoroalkylsulfonic and carboxylic acids in earthworms (Eisenia fetida): Accumulation and effects results from spiked soils at PFAS concentrations bracketing environmental relevance.

    Science.gov (United States)

    Karnjanapiboonwong, Adcharee; Deb, Sanjit K; Subbiah, Seenivasan; Wang, Degeng; Anderson, Todd A

    2018-05-01

    Effects of perfluorobutanesulfonic acid (PFBS), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluoroheptanoic acid (PFHpA) on earthworms (Eisenia fetida) in soils contaminated with these compounds at 0.1, 1, 10, 1,000, and 100,000 μg kg -1 dry weight, covering concentration levels found in background, biosolid-amended, and facility-surrounding soils, were investigated. Earthworms were exposed to spiked soil for 21 days. Concentrations of these compounds in earthworms after 21-d exposure ranged from below detection to 127 mg kg -1 wet weight with the rank order of PFNA > PFHxS > PFHpA > PFBS; no mortality of earthworms was observed in all treatments including controls, except PFBS at 1,000 μg kg -1 and all PFASs at 100,000 μg kg -1 . The highest weight loss (29%) was observed for earthworms exposed to PFNA at 100,000 μg kg -1 , which was significantly different from all other treatments except PFHpA at 100,000 μg kg -1 . These results are expected to fill some data gaps in toxicity of PFASs in terrestrial environments and provide helpful information on the potential for trophic transport of PFASs from soil to higher organisms. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Effects of an environmentally relevant concentration of diuron on oyster genitors during gametogenesis: responses of early molecular and cellular markers and physiological impacts.

    Science.gov (United States)

    Akcha, F; Barranger, A; Bachère, E; Berthelin, C Heude; Piquemal, D; Alonso, P; Sallan, R Rondon; Dimastrogiovanni, G; Porte, C; Menard, D; Szczybelski, A; Benabdelmouna, A; Auffret, M; Rouxel, J; Burgeot, T

    2016-04-01

    Genitors of the Pacific oyster Crassostrea gigas were submitted during gametogenesis to a short pulse exposure to the herbicide diuron at a realistic environmental concentration. Histological analysis showed no effect of diuron on gametogenesis course, sex ratio and reproductive effort. A non-significant increase in testosterone and progesterone levels was observed in genitors exposed to the herbicide. At cell level, diuron exposure was shown to modulate the phagocytic activity of circulating hemocytes. The results of a transcriptional analysis showed that diuron affected the expression of genes belonging to functions known to play a major role during oyster gametogenesis such as gene transcription regulation, DNA replication and repair, DNA methylation and cytokinesis. Taking into account the results we previously obtained on the same genitors, this study showed a negative effect of diuron on oyster reproduction by inducing both structural and functional modifications of the DNA.

  15. Cytogenetic and oxidative status of human lymphocytes after exposure to clinically relevant concentrations of antimalarial drugs atovaquone and proguanil hydrochloride in vitro.

    Science.gov (United States)

    Dinter, Domagoj; Gajski, Goran; Domijan, Ana-Marija; Garaj-Vrhovac, Vera

    2015-12-01

    Atovaquone (ATO) and proguanil hydrochloride (PROG) is the fixed combination for the prevention and treatment of Plasmodium falciparum malaria. As safe and effective antimalarial drugs are needed in both the treatment and the prophylaxis of malaria, this study was performed to investigate their possible cyto/genotoxic potential towards human lymphocytes and the possible mechanism responsible for it. Two different concentrations of ATO and PROG were used with and without S9 metabolic activation. The concentrations used were those found in human plasma when a fixed-dose combination of ATO and PROG was used: 2950/130 ng/mL after prophylactic treatment and 11 800/520 ng/mL after treatment of malaria, respectively. Possible cellular and DNA-damaging effects were evaluated by cell viability and alkaline comet assays, while oxidative stress potential was evaluated by formamidopyrimidine-DNA glycosylase (Fpg)-modified comet assay, in addition to measuring malondialdehyde and glutathione levels. According to our results, the ATO/PROG combination displayed only weak cyto/genotoxic potential towards human lymphocytes with no impact on oxidative stress parameters, suggesting that oxidative stress is not implicated in their mechanism of action towards human lymphocytes. Given that the key portion of the damaging effects was induced after S9 metabolic activation, it is to presume that the principal metabolite of PROG, cycloguanil, had the greatest impact. The obtained results indicate that the ATO/PROG combination is relatively safe for the consumption from the aspect of cyto/genotoxicity, especially if used for prophylactic treatment. Nevertheless, further cytogenetic research and regular patient monitoring are needed to minimize the risk of adverse events especially among frequent travellers. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  16. Molecular environment of stable iodine and radioiodine (129I) in natural organic matter: Evidence inferred from NMR and binding experiments at environmentally relevant concentrations

    Science.gov (United States)

    Xu, Chen; Zhong, Junyan; Hatcher, Patrick G.; Zhang, Saijin; Li, Hsiu-Ping; Ho, Yi-Fang; Schwehr, Kathleen A.; Kaplan, Daniel I.; Roberts, Kimberly A.; Brinkmeyer, Robin; Yeager, Chris M.; Santschi, Peter H.

    2012-11-01

    129I is a major by-product of nuclear fission and had become one of the major radiation risk drivers at Department of Energy (DOE) sites. 129I is present at elevated levels in the surface soils of the Savannah River Site (SRS) F-Area and was found to be bound predominantly to soil organic matter (SOM). Naturally bound 127I and 129I to sequentially extracted humic acids (HAs), fulvic acids (FAs) and a water extractable colloid (WEC) were measured in a 129I-contaminated wetland surface soil located on the SRS. WEC is a predominantly colloidal organic fraction obtained from soil re-suspension experiments to mimic the fraction that may be released during groundwater exfiltration, storm water or surface runoff events. For the first time, NMR techniques were applied to infer the molecular environment of naturally occurring stable iodine and radioiodine binding to SOM. Iodine uptake partitioning coefficients (Kd) by these SOM samples at ambient iodine concentrations were also measured and related to quantitative structural analyses by 13C DPMAS NMR and solution state 1H NMR on the eight humic acid fractions. By assessing the molecular environment of iodine, it was found that it was closely associated with the aromatic regions containing esterified products of phenolic and formic acids or other aliphatic carboxylic acids, amide functionalities, quinone-like structures activated by electron-donating groups (e.g., NH2), or a hemicellulose-lignin-like complex with phenyl-glycosidic linkages. However, FAs and WEC contained much greater concentrations of 127I or 129I than HAs. The contrasting radioiodine contents among the three different types of SOM (HAs, FAs and WEC) suggest that the iodine binding environment cannot be explained solely by the difference in the amount of their reactive binding sites. Instead, indirect evidence indicates that the macro-molecular conformation, such as the hydrophobic aliphatic periphery hindering the active aromatic cores and the hydrophilic

  17. Long-term exposure to gold nanoparticles accelerates larval metamorphosis without affecting mass in wood frogs (Lithobates sylvaticus) at environmentally relevant concentrations.

    Science.gov (United States)

    Fong, Peter P; Thompson, Lucas B; Carfagno, Gerardo L F; Sitton, Andrea J

    2016-09-01

    Nanoparticles are environmental contaminants of emerging concern. Exposure to engineered nanoparticles has been shown to have detrimental effects on aquatic organisms. The authors synthesized gold nanoparticles (18.1 ± 3.5 nm) and tested their effects on time to and weight at metamorphosis in wood frog (Lithobates sylvaticus) tadpoles, a species known to be sensitive to environmental stressors. Continuous exposure to all concentrations of gold nanoparticles (0.05 pM, 0.5 pM, and 5 pM in particles) for up to 55 d significantly reduced time to metamorphosis by as much as an average of 3 d (p metamorphosis. The approximately 18-nm gold nanoparticles used were metastable in dechlorinated tap water, resulting in a change in surface charge and aggregation over time, leading to negatively charged aggregates that were on the order of 60 nm to 110 nm. Nanoparticle aggregation could exacerbate the effect on time to metamorphosis. To the authors' knowledge, the present study is the first report on the effect of engineered nanoparticles of any kind on life-history variables in an amphibian, a taxonomic group that has been declining globally for at least 25 yr. Environ Toxicol Chem 2016;35:2304-2310. © 2016 SETAC. © 2016 SETAC.

  18. The influence of 5-HTTLPR genotype on the association between the plasma concentration and therapeutic effect of paroxetine in patients with major depressive disorder.

    Directory of Open Access Journals (Sweden)

    Tetsu Tomita

    Full Text Available The efficacy of treatment with selective serotonin reuptake inhibitors in patients with major depressive disorder (MDD can differ depending on the patient's serotonin transporter-linked polymorphic region (5-HTTLPR genotype, and the effects of varying plasma concentrations of drugs can also vary. We investigated the association between the paroxetine plasma concentration and clinical response in patients with different 5-HTTLPR genotypes.Fifty-one patients were enrolled in this study. The Montgomery-Asberg Depression Rating Scale (MADRS was used to evaluate patients at 0, 1, 2, 4, and 6 weeks. The patients' paroxetine plasma concentrations at week 6 were measured using high-performance liquid chromatography. Additionally, their 5-HTTLPR polymorphisms (alleles S and L were analyzed using a polymerase chain reaction with specific primers. We divided the participants into two groups based on their L haplotype: the SS group and the SL and LL group. We performed single and multiple regression analyses to investigate the associations between MADRS improvement and paroxetine plasma concentrations or other covariates for each group.There were no significant differences between the two groups with regard to demographic or clinical data. In the SS group, the paroxetine plasma concentration was significantly negatively correlated with improvement in MADRS at week 6. In the SL and LL group, the paroxetine plasma concentration was significantly positively correlated with improvement in MADRS at week 6 according to the results of the single regression analysis; however, it was not significantly correlated with improvement in MADRS at week 6 according to the results of the multiple regression analysis.Among patients with MDD who do not respond to paroxetine, a lower plasma concentration or a lower oral dose of paroxetine might be more effective in those with the SS genotype, and a higher plasma concentration might be more effective in those with the SL or LL

  19. Stabilisation goals for concentrations of climate-relevant gaseous emissions: Effects and emission pathways. Final report; Stabilisierungsziele fuer Treibhausgaskonzentrationen: Eine Abschaetzung der Auswirkungen und der Emissionspfade. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Onigkeit, J.; Alcamo, J.; Kaspar, F.; Roesch, T.

    2000-04-01

    Two different stabilisation goals were assumed, i.e. 550 ppm and 450 ppm of carbon dioxide. First, the global anthropogenic carbon dioxide emissions were calculated that are permissible to reach these goals. Secondly, the global and regional environmental effects of these concentration goals were assessed. In this, carbon dioxide, nitric oxides and methane emissions from power generation, industry and agriculture were considered. Apart from an investigation of the global reduction strategies required, a key was developed for sharing the global reduction loads between Annex B countries and non-Annex B countries. To reach a stable concentration of 550 ppm carbon dioxide in the atmosphere, the global anthropogenic carbon dioxide emissions per annum may increase slightly until 2030 but must be lowered to the 1990 level by 2100. In the case of 450 ppm, the 1990 level must even be halved by 2100. The consequences of climate change for agriculture, natural vegetation, availability of water, and sea levels were investigated in consideration of regional variations in carbon dioxide emissions and emission reduction measures. In spite of extensive emission control, the area of reduced agricultural productivity will grow rapidly in both cases, and natural vegetation will be endangered, although with strong regional variations. [German] Ausgehend von zwei langfristigen Klimaschutzzielen (Stabilisierung der atmosphaerischen CO{sub 2}-Konzentration bei 550 ppm und bei 450 ppm) wurde mit Hilfe des IMAGE 2.1 Modells: (1) Eine Berechnung der globalen anthropogenen Treibhausgasemissionen durchgefuehrt, die zwischen 1990 und 2100 erlaubt sind, um diese Konzentrationsziele zu erreichen. (2) Wurde eine Abschaetzung der globalen und regionalen Umweltauswirkungen durch den Klimawandel durchgefuehrt, der mit diesen Konzentrationszielen einhergeht. Bei der Analyse wurden CO{sub 2}-, N{sub 2}O- und CH{sub 4} Emissionen aus dem Energie/Industrie- und dem landwirtschaftlichen Sektor

  20. Determination of the Minimal Fresh Gas Flow to Maintain a Therapeutic Inspired Oxygen Concentration in a Semi-Closed Anesthesia Circle System Using an Oxygen Concentrator as the Oxygen Source

    National Research Council Canada - National Science Library

    Grano, Joan

    2001-01-01

    The purpose of this study was to determine the rate of oxygen dilution, resulting from argon accumulation, using 3 low fresh gas flow rates using an oxygen concentrator in a semi-closed anesthesia circle system...

  1. Relation between CYP2D6 Genotype, Phenotype and Therapeutic Drug Concentrations among Nortriptyline and Venlafaxine Users in Old Age Psychiatry

    NARCIS (Netherlands)

    Berm, E; Kok, R.; Hak, E; Wilffert, B

    2016-01-01

    Objectives: To determine relations between drug concentrations and the cytochrome P450-CYP2D6 genotype or phenotype among elderly patients treated with nortriptyline or venlafaxine. Methods: A post-hoc analysis of a clinical trial was performed. Patients were grouped into phenotypes according to the

  2. Clinical Relevance of Adipokines

    Directory of Open Access Journals (Sweden)

    Matthias Blüher

    2012-10-01

    Full Text Available The incidence of obesity has increased dramatically during recent decades. Obesity increases the risk for metabolic and cardiovascular diseases and may therefore contribute to premature death. With increasing fat mass, secretion of adipose tissue derived bioactive molecules (adipokines changes towards a pro-inflammatory, diabetogenic and atherogenic pattern. Adipokines are involved in the regulation of appetite and satiety, energy expenditure, activity, endothelial function, hemostasis, blood pressure, insulin sensitivity, energy metabolism in insulin sensitive tissues, adipogenesis, fat distribution and insulin secretion in pancreatic β-cells. Therefore, adipokines are clinically relevant as biomarkers for fat distribution, adipose tissue function, liver fat content, insulin sensitivity, chronic inflammation and have the potential for future pharmacological treatment strategies for obesity and its related diseases. This review focuses on the clinical relevance of selected adipokines as markers or predictors of obesity related diseases and as potential therapeutic tools or targets in metabolic and cardiovascular diseases.

  3. [Music as adjuvant therapy for coronary heart disease. Therapeutic music lowers anxiety, stress and beta-endorphin concentrations in patients from a coronary sport group].

    Science.gov (United States)

    Vollert, J O; Störk, T; Rose, M; Möckel, M

    2003-12-19

    In a study with coronary patients it was estimated that music is able to lower stress and fear and contributing to relaxation in spite of physical exercise. 15 patients (13 male, two female, mean age 62,2 +/- 7,6 years) of a coronary sport unit were listening to an especially composed relaxation music while training their common heart-frequency adapted exercises. Before the exercises and after listening to music blood pressures were measured and blood was collected for determination of beta-endorphin. Simultaneous to blood collection the participants had to perform two psychometric test: the perceived stress experience questionnaire (PSQ) of Levenstein to measure the graduation of subjective perceived stress and the state-anxiety inquiry (STAI) of Spielberger as an indicator of coping. To practice the trial ("test trial"), the whole protocol was performed one week prior to the mean trial, but without listening to music and without blood collections and blood pressure measurements. In the test trial without music there were no significant changes in PSQ-data. In the mean trial, under the influence of music, values in the section "worries" decreased as a sign of lower worries (26.6 versus 27.6; p = 0.039). STAI-values were significantly lower as a sign of reduced fear after listening to music (31 versus 34; p = 0.045). beta-endorphin concentration (10.91 microg/l versus 15.96 microg/l, p = 0.044) and systolic blood pressure (130 mmHg versus 140 mmHg; p = 0.007) decreased significantly after listening to music. Regarding worries and fear, patients seemed to benefit by the intervention of music. beta-endorphin was lowered significantly after music despite physical activity.

  4. Macromolecular therapeutics.

    Science.gov (United States)

    Yang, Jiyuan; Kopeček, Jindřich

    2014-09-28

    This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines - (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Therapeutic drug monitoring of antimicrobials

    Science.gov (United States)

    Roberts, Jason A; Norris, Ross; Paterson, David L; Martin, Jennifer H

    2012-01-01

    Optimizing the prescription of antimicrobials is required to improve clinical outcome from infections and to reduce the development of antimicrobial resistance. One such method to improve antimicrobial dosing in individual patients is through application of therapeutic drug monitoring (TDM). The aim of this manuscript is to review the place of TDM in the dosing of antimicrobial agents, specifically the importance of pharmacokinetics (PK) and pharmacodynamics (PD) to define the antimicrobial exposures necessary for maximizing killing or inhibition of bacterial growth. In this context, there are robust data for some antimicrobials, including the ratio of a PK parameter (e.g. peak concentration) to the minimal inhibitory concentration of the bacteria associated with maximal antimicrobial effect. Blood sampling of an individual patient can then further define the relevant PK parameter value in that patient and, if necessary, antimicrobial dosing can be adjusted to enable achievement of the target PK/PD ratio. To date, the clinical outcome benefits of a systematic TDM programme for antimicrobials have only been demonstrated for aminoglycosides, although the decreasing susceptibility of bacteria to available antimicrobials and the increasing costs of pharmaceuticals, as well as emerging data on pharmacokinetic variability, suggest that benefits are likely. PMID:21831196

  6. Proceso de Cambio Psicoterapéutico: Análisis de Episodios Relevantes en una Terapia Grupal con Pacientes Adictos Therapeutic Change Process: Analysis of Relevant Episodes in a Group Therapy With Addict Patients

    Directory of Open Access Journals (Sweden)

    Nelson Valdés

    2005-11-01

    Full Text Available En el presente artículo se presentan los resultados de una investigación que tuvo como objetivo determinar y describir el tipo de acciones comunicacionales realizadas por terapeutas y pacientes durante las sesiones de una terapia grupal. Para esto se utilizó una metodología orientada al descubrimiento empleando un análisis cualitativo de contenido. En los resultados se incluye tanto la descripción de las acciones identificadas de acuerdo al nivel de análisis, así como los patrones ideales de secuencia de dichos componentes asociados al cambio y propios de esta modalidad terapéutica. Finalmente, los resultados son discutidos considerando los principales antecedentes teóricos y empíricos en materia de investigación en psicoterapia.This article presents the results of a study aimed to determine and describe the type of communicative actions made by therapists and patients during the sessions of a group therapy. A discovery-oriented methodology was applied, conducting qualitative content analysis. Results include the description of the identified actions by levels of analysis, and their ideal sequential patterns, associated to in-session change and particularly to this therapeutic modality. Finally, the results are discussed considering the main theoretical and empirical frameworks in psychotherapy research.

  7. In vitro killing of Escherichia coli, Staphylococcus pseudintermedius and Pseudomonas aeruginosa by enrofloxacin in combination with its active metabolite ciprofloxacin using clinically relevant drug concentrations in the dog and cat.

    Science.gov (United States)

    Blondeau, J M; Borsos, S; Blondeau, L D; Blondeau, B J

    2012-03-23

    Enrofloxacin is a fluoroquinolone antibacterial agent used to treat infections in companion animals. Enrofloxacin's antimicrobial spectrum includes Gram positive and Gram-negative bacteria and demonstrates concentration-dependent bacteriocidal activity. In dogs and cats, enrofloxacin is partially metabolized to ciprofloxacin and both active agents circulate simultaneously in treated animals at ratios of approximately 60-70% enrofloxacin to 30-40% ciprofloxacin. We were interested in determining the killing of companion animal isolates of Escherichia coli, Staphylococcus pseudintermedius and Pseudomonas aeruginosa by enrofloxacin and ciprofloxacin combined using clinically relevant drug concentrations and ratios. For E. coli isolates exposed to 2.1 and 4.1μg/ml of enrofloxacin/ciprofloxacin at 50:50, 60:40 and 70:30 ratios, a 1.7-2.5log(10) reduction (94-99% kill) was seen following 20min of drug exposure; 0.89-1.7log(10) (92-99% kill) of S. pseudintermedius following 180min of drug exposure; 0.85-3.4log(10) (98-99% kill) of P. aeruginosa following 15min of drug exposure. Killing of S. pseudintermedius was enhanced in the presence of enrofloxacin whereas killing of P. aeruginosa was enhanced in the presence of ciprofloxacin. Antagonism was not seen when enrofloxacin and ciprofloxacin were used in kill assays. The unique feature of partial metabolism of enrofloxacin to ciprofloxacin expands the spectrum of enhanced killing of common companion animal pathogens. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Therapeutic ultrasound

    International Nuclear Information System (INIS)

    Crum, Lawrence A

    2004-01-01

    The use of ultrasound in medicine is now quite commonplace, especially with the recent introduction of small, portable and relatively inexpensive, hand-held diagnostic imaging devices. Moreover, ultrasound has expanded beyond the imaging realm, with methods and applications extending to novel therapeutic and surgical uses. These applications broadly include: tissue ablation, acoustocautery, lipoplasty, site-specific and ultrasound mediated drug activity, extracorporeal lithotripsy, and the enhancement of natural physiological functions such as wound healing and tissue regeneration. A particularly attractive aspect of this technology is that diagnostic and therapeutic systems can be combined to produce totally non-invasive, imageguided therapy. This general lecture will review a number of these exciting new applications of ultrasound and address some of the basic scientific questions and future challenges in developing these methods and technologies for general use in our society. We shall particularly emphasize the use of High Intensity Focused Ultrasound (HIFU) in the treatment of benign and malignant tumors as well as the introduction of acoustic hemostasis, especially in organs which are difficult to treat using conventional medical and surgical techniques. (amum lecture)

  9. A Wnt1 regulated Frizzled-1/β-Catenin signaling pathway as a candidate regulatory circuit controlling mesencephalic dopaminergic neuron-astrocyte crosstalk: Therapeutical relevance for neuron survival and neuroprotection

    Directory of Open Access Journals (Sweden)

    Pluchino Stefano

    2011-07-01

    /β-catenin antagonist within the SN induces reactive astrocytosis and acutely inhibits TH+ neuron survival in ipsilateral SNpc, an effect efficiently prevented by pharmacological activation of β-catenin signaling within the SNpc. Conclusion These results defining a novel Wnt1/Fzd-1/β-catenin astrocyte-DA autoprotective loop provide a new mechanistic inside into the regulation of pro-survival processes, with potentially relevant consequences for drug design or drug action in Parkinson's disease.

  10. [End therapeutic nihilism towards COPD].

    Science.gov (United States)

    Juergens, Uwe R

    2007-03-15

    Prevention of COPD requires appropriate patient education, especially of adolescents, as well as the establishment of an effective national health policy. The new GOLD guidelines represent the current standard of knowledge on the management of chronic, progressive, obstructive pulmonary diseases. It points out that COPD is avoidable and treatable,and hence, there is no reason for therapeutic nihilism. Chronic bronchitis preceding a progressive respiratory obstruction cannot be improved with the presently available respiratory therapeutics. For this reason, therapeutic measures concentrate on the avoidance of exacerbations, which are primarily responsible for the severity of the course of COPD.

  11. Clinical research of FK506 therapeutic window concentration in renal transplant recipients%肾移植受者应用他克莫司治疗窗浓度的探讨

    Institute of Scientific and Technical Information of China (English)

    王立明; 闵志廉; 朱有华; 高春芳; 陆慧琦; 周梅生; 姚亚成

    2000-01-01

    目的 寻求适合国人肾移植受者他克莫司(FK506)理想治疗窗浓度范围.方法 应用微粒子酶免疫分析法测定58例肾移植患者口服FK506后12 h的血药谷浓度,并观察排斥反应的发生及药物的肾毒性.结果 FK506的血药浓度,术后1个月为(13.0±2.1)μg/L,2~3个月为(9.4±1.6)μg/L,3个月以后为(6.5±1.3)μg/L,比较各时期全血FK506谷浓度,差异均有极显著性(P<0.01);术后发生急性排斥反应3例次,肾毒性4例次.结论 FK506具有良好的免疫抑制效果,其治疗窗浓度范围,术后第1个月为11~15μg/L,第2~3个月为8~11μg/L;第3个月后为5~8μg/L,此浓度范围既能达到满意的免疫抑制效果,又能减少FK506的肾毒性.%Objective In order to search for the proper therapeutic window concentration of FK506 in Chinese renal transplant recipients.Methods The FK506 trough level 12 h after oral administration in 58 renal transplantation patients was assayed by means of MEIA.The occurrence of rejection and the drug toxicity were observed.Results The blood FK506 trough level was(13.0±2.1)μg/L within the first month,(9.4±1.6)μg/L within second to third months,and(6.5±1.3)μg/L from the third month after transplantation with the difference among the different intervals being very significant(P<0.01).There were 3 case-times of acute rejection and 4 case-times of renal toxicity.Conclusions The whole blood FK506 trough level was 11~15μg/L within the first month,8~11μg/L within the second and third month,5~8μg/L from the fourth month after transplantation.This range of therapeutic window concentration of FK506 trough levels was ideal for Chinese renal transplant recipients with less acute rejection and toxicity effects on kidney.

  12. TU-H-CAMPUS-TeP3-04: Probing the Dose Enhancement Due to a Clinically-Relevant Concentration of Gold Nanoparticles and Yb-169 Gamma Rays Using PRESAGE Dosimeters

    Energy Technology Data Exchange (ETDEWEB)

    Cho, J [UT MD Anderson Cancer Center, Houston, TX (United States); Oklahoma State University, Stillwater, OK (United States); Alqathami, M; Cho, S [UT MD Anderson Cancer Center, Houston, TX (United States); Reynoso, F [UT MD Anderson Cancer Center, Houston, TX (United States); Washington University School of Medicine, St. Louis, MO (United States)

    2016-06-15

    Purpose: To probe physical evidences of the dose enhancement due to a low/clinically-relevant concentration of gold nanoparticles (GNPs) and Yb-169 gamma rays using PRESAGE dosimeters. Methods: A PRESAGE cuvette was placed at approximately 2 mm above the plane containing three novel Yb-169 brachytherapy seeds (3.2, 3.2, and 5.3 mCi each). Two types of PRESAGE dosimeters were used – plain PRESAGEs (controls) and PRESAGEs loaded with 0.02 wt. % of GNPs (GNP-PRESAGEs). Each PRESAGE dosimeter was irradiated with different time durations (0 to 24 hours) to deliver 0, 4, 8, 16 and 24 Gy of dose. For a reference/comparison, both types of PRESAGEs were also irradiated using 250 kVp x-rays with/without Er-filter to deliver 0, 3, 10, and 30 Gy of dose. Er-filter was used to emulate Yb-169 spectrum using 250 kVp x-rays. The absorption spectra of PRESAGEs were measured using a UV spectrophotometer and used to determine the corresponding optical densities (ODs). Results: GNP-PRESAGEs exposed to Yb-169 sources showed ∼65% increase in ODs compared with controls. When exposed to Er-filtered and unfiltered 250 kVp x-rays, they produced smaller increases in ODs, ∼41% and ∼37%, respectively. There was a linear relationship between ODs and delivered doses with a goodness-of-fit (R2) greater than 0.99. Conclusion: A notable increase in the ODs (∼65%) was observed for GNP-PRESAGEs irradiated by Yb-169 gamma rays. Considering the observed OD increases, it was highly likely that Yb-169 gamma rays were more effective than both Er-filtered and unfiltered 250 kVp x-rays, in terms of producing the dose enhancement. Due to several unknown factors (e.g., possible difference in the dose response of GNP-PRESAGEs vs. PRESAGEs), however, a further investigations is necessary to establish the feasibility of quantifying the exact amount of macroscopic or microscopic/local GNP-mediated dose enhancement using PRESAGE or similar volumetric dosimeters. Supported by DOD/PCRP grant W81XWH-12

  13. Why relevance theory is relevant for lexicography

    DEFF Research Database (Denmark)

    Bothma, Theo; Tarp, Sven

    2014-01-01

    This article starts by providing a brief summary of relevance theory in information science in relation to the function theory of lexicography, explaining the different types of relevance, viz. objective system relevance and the subjective types of relevance, i.e. topical, cognitive, situational...... that is very important for lexicography as well as for information science, viz. functional relevance. Since all lexicographic work is ultimately aimed at satisfying users’ information needs, the article then discusses why the lexicographer should take note of all these types of relevance when planning a new...... dictionary project, identifying new tasks and responsibilities of the modern lexicographer. The article furthermore discusses how relevance theory impacts on teaching dictionary culture and reference skills. By integrating insights from lexicography and information science, the article contributes to new...

  14. Effect of therapeutic concentration of lithium on live HEK293 cells; increase of Na+/K+-ATPase, change of overall protein composition and alteration of surface layer of plasma membrane.

    Science.gov (United States)

    Vosahlikova, Miroslava; Ujcikova, Hana; Chernyavskiy, Oleksandr; Brejchova, Jana; Roubalova, Lenka; Alda, Martin; Svoboda, Petr

    2017-05-01

    The effect of long-term exposure of live cells to lithium cations (Li) was studied in HEK293 cells cultivated in the presence of 1mM LiCl for 7 or 21days. The alteration of Na + /K + -ATPase level, protein composition and biophysical state of plasma membrane was determined with the aim to characterize the physiological state of Li-treated cells. Na + /K + -ATPase level was determined by [ 3 H]ouabain binding and immunoblot assays. Overall protein composition was determined by 2D electrophoresis followed by proteomic analysis by MALDI-TOF MS/MS and LFQ. Li interaction with plasma membrane was characterized by fluorescent probes DPH, TMA-DPH and Laurdan. Na + /K + -ATPase was increased in plasma membranes isolated from cells exposed to Li. Identification of Li-altered proteins by 2D electrophoresis, MALDI-TOF MS/MS and LFQ suggests a change of energy metabolism in mitochondria and cytosol and alteration of cell homeostasis of calcium. Measurement of Laurdan generalized polarization indicated a significant alteration of surface layer of isolated plasma membranes prepared from both types of Li-treated cells. Prolonged exposure of HEK293 cells to 1mM LiCl results in up-regulation of Na + /K + -ATPase expression, reorganization of overall cellular metabolism and alteration of the surface layer/polar head-group region of isolated plasma membranes. Our findings demonstrate adaptation of live HEK293 cell metabolism to prolonged exposure to therapeutic concentration of Li manifested as up-regulation of Na + /K + -ATPase expression, alteration of protein composition and change of the surface layer of plasma membrane. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Therapeutic relevance of HRCT findings from a pneumological viewpoint

    International Nuclear Information System (INIS)

    Suchy, R.; Pfeifer, M.

    2014-01-01

    The high-resolution computed tomography (HRCT) technique is an essential component in diagnosing interstitial lung disease (ILD) as it provides important and specialized information and a much greater accuracy than chest X-rays. It contributes to a narrowing down of the differential diagnoses and is also important for planning further invasive investigations, e.g. bronchoscopy, bronchoalveolar lavage, transbronchial lung biopsy and surgical lung biopsy, if needed. An accurate diagnosis of ILD is based on a multidisciplinary discussion involving pulmonologists, radiologists and pathologists experienced in the diagnosis of ILD. The therapy approaches of five different entities of ILD are shown as examples. In hypersensitivity pneumonitis the mainstay of treatment is complete avoidance of exposure to the provoking antigen. In cryptogenic organizing pneumonia most patients recover with corticosteroid therapy with prednisolone over a period of 6 months to 1 year. In cases of sarcoidosis therapy depends on organ involvement and functional impairment but there is no durable benefit to routine treatment of patients with acute pulmonary sarcoidosis, even among those with stage II or III chest radiographs. In general, patients with severe or progressive disease will require treatment. In idiopathic pulmonary fibrosis (IPF) a confident radiological diagnosis of definitive usual interstitial pneumonia (UIP) obviates the need for surgical lung biopsy. Other etiologies of a HRCT pattern of UIP, such as domestic and occupational environmental exposure, connective tissue disease and drug toxicity must be ruled out. In IPF antifibrotic therapy with pirfenidone (approval since 2011) or the triple tyrosine kinase inhibitor nintendanib (pending approval in 2015) can reduce disease progression but therapy with acetylcysteine alone or in combination with prednisolone and azathioprine failed to meet efficacy endpoints. In the management of scleroderma associated ILD rapid semiquantitative evaluation of the extent of the disease on HRCT > 20 % is useful for identifying patients who require treatment. (orig.) [de

  16. A therapeutic community as a relevant and efficient ecclesial model ...

    African Journals Online (AJOL)

    2016-07-15

    Jul 15, 2016 ... doctors, sangomas and prophets to ensure that their health and that of their .... in the sense of acknowledgment, appreciation and respect. Heimbrock .... A thorough critical introspection by the African church in this at ..... theology: Only study guide for CGM112P, University of South Africa, Pretoria. Uka, E.M. ...

  17. Pulmonary embolism. Clinical relevance, requirements for diagnostic and therapeutic strategies

    International Nuclear Information System (INIS)

    Nowak, F.G.; Halbfass, P.; Hoffmann, E.

    2007-01-01

    In the population the annual incidence of pulmonary embolism amounts to 1.3-2.8 per 1000 at the age of 65-89 years. Mortality reaches about 17% within the first 3 months. Acute pulmonary embolism is characterized by an increase in pulmonary arterial pressure and an impairment of the pulmonary gas exchange. Elevation of the right cardiac pressure up to right heart decompensation may follow. In addition, hypoxemia, hyperventilation, dead space ventilation, right to left shunting, bronchoconstriction, and vasoconstriction may occur. Clinical examination, ECG, laboratory findings such as elevated D-dimer, blood gas analysis, ultrasound examination of the veins of the lower extremities, and transthoracic echocardiography are acutely available diagnostic methods of an emergency department. In addition, extensive diagnostic procedures like pulmonary scintigraphy and pulmonary angiography may be required. The aim is to get a definite diagnosis as quickly as possible to direct therapy. In acute pulmonary embolism with cardiac shock, monitoring and stabilization of the circulatory function as well as an appropriate anticoagulant therapy are essential. In some cases surgery or a local fibrinolytic intervention is indicated. (orig.) [de

  18. Deep learning relevance

    DEFF Research Database (Denmark)

    Lioma, Christina; Larsen, Birger; Petersen, Casper

    2016-01-01

    train a Recurrent Neural Network (RNN) on existing relevant information to that query. We then use the RNN to "deep learn" a single, synthetic, and we assume, relevant document for that query. We design a crowdsourcing experiment to assess how relevant the "deep learned" document is, compared...... to existing relevant documents. Users are shown a query and four wordclouds (of three existing relevant documents and our deep learned synthetic document). The synthetic document is ranked on average most relevant of all....

  19. Antibody Engineering and Therapeutics

    Science.gov (United States)

    Almagro, Juan Carlos; Gilliland, Gary L; Breden, Felix; Scott, Jamie K; Sok, Devin; Pauthner, Matthias; Reichert, Janice M; Helguera, Gustavo; Andrabi, Raiees; Mabry, Robert; Bléry, Mathieu; Voss, James E; Laurén, Juha; Abuqayyas, Lubna; Barghorn, Stefan; Ben-Jacob, Eshel; Crowe, James E; Huston, James S; Johnston, Stephen Albert; Krauland, Eric; Lund-Johansen, Fridtjof; Marasco, Wayne A; Parren, Paul WHI; Xu, Kai Y

    2014-01-01

    The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates. PMID:24589717

  20. Therapeutic and diagnostic nanomaterials

    CERN Document Server

    Devasena T

    2017-01-01

    This brief highlights nanoparticles used in the diagnosis and treatment of prominent diseases and toxic conditions. Ecofriendly methods which are ideal for the synthesis of medicinally valued nanoparticles are explained and the characteristic features of these particles projected. The role of these particles in the therapeutic field, and the induced biological changes in some diseases are discussed. The main focus is on inflammation, oxidative stress and cellular membrane integrity alterations. The effect of nanoparticles on these changes produced by various agents are highlighted using in vitro and in vivo models. The mechanism of nanoparticles in ameliorating the biological changes is supported by relevant images and data. Finally, the brief demonstrates recent developments on the use of nanoparticles in diagnosis or sensing of some biological materials and biologically hazardous environmental materials.

  1. Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer's disease.

    Science.gov (United States)

    Barage, Sagar H; Sonawane, Kailas D

    2015-08-01

    Alzheimer's disease is an irreversible, progressive neurodegenerative disorder. Various therapeutic approaches are being used to improve the cholinergic neurotransmission, but their role in AD pathogenesis is still unknown. Although, an increase in tau protein concentration in CSF has been described in AD, but several issues remains unclear. Extensive and accurate analysis of CSF could be helpful to define presence of tau proteins in physiological conditions, or released during the progression of neurodegenerative disease. The amyloid cascade hypothesis postulates that the neurodegeneration in AD caused by abnormal accumulation of amyloid beta (Aβ) plaques in various areas of the brain. The amyloid hypothesis has continued to gain support over the last two decades, particularly from genetic studies. Therefore, current research progress in several areas of therapies shall provide an effective treatment to cure this devastating disease. This review critically evaluates general biochemical and physiological functions of Aβ directed therapeutics and their relevance. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Thyroid abnormalities after therapeutic external radiation

    International Nuclear Information System (INIS)

    Hancock, Steven L.; McDougall, I. Ross; Constine, Louis S.

    1995-01-01

    The thyroid gland is the largest pure endocrine gland in the body and one of the organs most likely to produce clinically significant abnormalities after therapeutic external radiation. Radiation doses to the thyroid that exceed approximately 26 Gy frequently produce hypothyroidism, which may be clinically overt or subclinical, as manifested by increased serum thyrotropin and normal serum-free thyroxine concentrations. Pituitary or hypothalamic hypothyroidism may arise when the pituitary region receives doses exceeding 50 Gy with conventional, 1.8-2 Gy fractionation. Direct irradiation of the thyroid may increase the risk of Graves' disease or euthyroid Graves' opthalmopathy. Silent thyroiditis, cystic degeneration, benign adenoma, and thyroid cancer have been observed after therapeutically relevant doses of external radiation. Direct or incidental thyroid irradiation increases the risk for well-differentiated, papillary, and follicular thyroid cancer from 15- to 53-fold. Thyroid cancer risk is highest following radiation at a young age, decreases with increasing age at treatment, and increases with follow-up duration. The potentially prolonged latent period between radiation exposure and the development of thyroid dysfunction, thyroid nodularity, and thyroid cancer means that individuals who have received neck or pituitary irradiation require careful, periodic clinical and laboratory evaluation to avoid excess morbidity

  3. Thyroid abnormalities after therapeutic external radiation

    Energy Technology Data Exchange (ETDEWEB)

    Hancock, S.L.; McDougall, I.R. [Stanford Univ. School of Medicine, Stanford, CA (United States); Constine, L.S. [Strong Memorial Hospital, Rochester, NY (United States)

    1995-03-30

    The thyroid gland is the largest pure endocrine gland in the body and one of the organs most likely to produce clinically significant abnormalities after therapeutic external radiation. Radiation doses to the thyroid that exceed approximately 26 Gy frequently produce hypothyroidism, which may be clinically overt or subclinical, as manifested by increased serum thyrotropin and normal serum-free thyroxine concentrations. Pituitary or hypothalamic hypothyroidism may arise when the pituitary region receives doses exceeding 50 Gy with conventional, 1.8-2 Gy fractionation. Direct irradiation of the thyroid may increase the risk of Graves` disease or euthyroid Graves` ophthalmopathy. Silent thyroiditis, cystic degeneration, benign adenoma, and thyroid cancer have been observed after therapeutically relevant doses of external radiation. Direct or incidental thyroid irradiation increases the risk for well-differentiated, papillary, and follicular thyroid cancer from 15- to 53-fold. Thyroid cancer risk is highest following radiation at a young age, decreases with increasing age at treatment, and increases with follow-up duration. The potentially prolonged latent period between radiation exposure and the development of thyroid dysfunction, thyroid nodularity, and thyroid cancer means that individuals who have received neck or pituitary irradiation require careful, periodic clinical and laboratory evaluation to avoid excess morbidity. 39 refs.

  4. Up-regulation of visfatin expression in subjects with hyperthyroidism and hypothyroidism is partially relevant to a nonlinear regulation mechanism between visfatin and tri-iodothyronine with various concentrations.

    Science.gov (United States)

    Han, Jing; Zhang, Tian-ou; Xiao, Wen-hua; Chang, Cui-qing; Ai, Hua

    2012-03-01

    Visfatin, a visceral fat-derived adipocytokine, plays a significant physiological function in lipid metabolism. However, the precise function of visfatin and its regulation by thyroid hormones are still unknown. This study observed the plasma visfatin concentrations in subjects with hyperthyroidism and hypothyroidism in vivo, and investigated the possible regulation mechanism between visfatin and tri-iodothyronine (T3) in vitro as a further interpretation. The experiment in vivo included clinical subjects (57 patients with thyroid dysfunction and 29 euthyroid healthy volunteers) and an animal model (24 Wistar rats). All subjects were divided into hyperthyroidism, hypothyroidism and euthyroidism groups, with plasma thyroid hormones, thyrotropin, visfatin and triglyceride concentrations determined. Visfatin mRNA expression in visceral fat and liver of rats was detected by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). The experiment in vitro studied 3T3-L1 cells and visfatin mRNA expression under nine different T3 concentrations (0, 0.1, 0.25, 0.5, 1, 5, 10, 20, 100 nmol/L) using quantitative real-time RT-PCR. Clinical subjects and animal models showed elevated plasma visfatin concentrations in the hyperthyroidism group (20.466 ng/ml (15.263, 26.795 ng/ml) and (1209.164±165.292) ng/L) and hypothyroidism group (12.457 ng/ml (11.115, 15.454 ng/ml) and (1205.425±109.200) ng/L) compared to euthyroidism group (6.891 ng/ml (5.888, 8.803 ng/ml) and (926.650±54.002) ng/L, Phyperthyroidism and hypothyroidism groups increased about 3.33-fold and 1.98-fold compared to the euthyroidism group (P0.05) and correlation (r=0.121, P=0.572) was found in the liver. T3 induced a remarkable increase of visfatin mRNA expression in 3T3-L1 cells at low concentrations (0-0.5 nmol/L T3) followed by a sharp decrease at higher concentrations (0.5-100 nmol/L T3), with an inflection point at 0.5 nmol/L T3. Elevated circulating visfatin levels in subjects with

  5. Therapeutic drug monitoring of aminoglycosides in neonates

    NARCIS (Netherlands)

    Touw, Daniël J; Westerman, Elsbeth M; Sprij, Arwen J

    2009-01-01

    The efficacy and toxicity of aminoglycosides show a strong direct positive relationship with blood drug concentrations, therefore, therapy with aminoglycosides in adults is usually guided by therapeutic drug monitoring. Dosing regimens in adults have evolved from multiple daily dosing to

  6. Variáveis relevantes no processo terapêutico para a aquisição do onset complexo na fala de crianças com desvio fonológico Relevant variables in the therapeutic process for the consonant clusters acquisition in the speech of children with phonological disorder

    Directory of Open Access Journals (Sweden)

    Vanessa Giacchini

    2012-01-01

    Full Text Available OBJETIVO: apresentar variáveis relevantes no processo terapêutico de aquisição do onset complexo (OC em crianças que realizam a simplificação dessa estrutura. MÉTODO: participaram do estudo quatro crianças com diagnóstico de desvio fonológico (DF, com idades entre 5:4 a 7:7, que utilizavam a estratégia de alongamento compensatório (EAC, possuíam [r] e [l] no seu inventário fonético e realizavam a simplificação do OC. As crianças foram submetidas a diferentes modelos terapêuticos e, a partir dos dados obtidos nas sondagens, realizaram-se análises das variáveis linguísticas e extralinguísticas relevantes durante o processo terapêutico. A análise dos dados de fala foram realizadas por meio do programa estatístico VARBRUL. RESULTADOS: a variável gravidade do desvio foi a que o programa selecionou como relevante para a produção correta do OC, para sua simplificação e para a distorção da líquida da estrutura. Ele apontou que quando o sujeito é submetido à terapia articulatória (TA, há maior probabilidade de ocorrência de produção correta de CCV, realização de distorção e metátese. O fonema /d/ se mostrou favorecedor da estratégia de metátese. A substituição da líquida foi influenciada pela variável sujeito e pelo tipo de líquida formadora do OC. CONCLUSÃO: quanto às variáveis, a gravidade do DF mostra-se importante tanto para o sucesso da terapia (produção correta de CCV, como para o uso de estratégias de reparo. Observou-se que aplicar tipos de terapia distintos faz com que as crianças respondam de forma diferenciada a cada um deles, com melhor desempenho na TA.PURPOSE: to provide relevant variable aspects in the therapeutic process of consonant clusters (CC acquisition in children but maintains the CCV simplification. METHOD: four children diagnosed with phonological disorders, aged 5:4 to 7:7 took part in the study, using the strategy of compensatory lengthening, having [r] and [l] in the

  7. Relevance of nanotechnology to Africa: synthesis, applications and safety

    CSIR Research Space (South Africa)

    Musee, N

    2012-07-01

    Full Text Available In this chapter, two nanotechnology-based applications relevant to Africa in promoting sustainability and achievement of the Millennium Development Goals (MDGs) are presented. The applications comprise the provision of therapeutic treatment...

  8. Purified deoxynivalenol or feed restriction reduces mortality in rainbow trout, Oncorhynchus mykiss (Walbaum), with experimental bacterial coldwater disease but biologically relevant concentrations of deoxynivalenol do not impair the growth of Flavobacterium psychrophilum.

    Science.gov (United States)

    Ryerse, I A; Hooft, J M; Bureau, D P; Hayes, M A; Lumsden, J S

    2015-09-01

    Diets containing deoxynivalenol (DON) were fed to rainbow trout Oncorhynchus mykiss (Walbaum) for 4 weeks followed by experimental infection (intraperitoneal) with Flavobacterium psychrophilum (4.1 × 10(6) colony-forming units [CFU] mL(-1) ). Mortality of rainbow trout fed either 6.4 mg kg(-1) DON or trout pair-fed the control diet was significantly reduced (P trout fed the control diet to apparent satiation (trout were fed one of three experimental diets; a control diet, a diet produced with corn naturally contaminated with DON (3.3 mg kg(-1) DON) or a diet containing purified DON (3.8 mg kg(-1) ); however, these fish were not experimentally infected. The presence of DON resulted in significant reduction (P trout fed diets containing purified DON (3.8 mg kg(-1) ) was significantly higher (P < 0.05) at 35 day post-exposure compared with controls. The antimicrobial activity of DON was examined by subjecting F. psychrophilum in vitro to serial dilutions of the chemical. Complete inhibition occurred at a concentration of 75 mg L(-1) DON, but no effect was observed below this concentration (0-30 mg L(-1) ). © 2014 John Wiley & Sons Ltd.

  9. Making Deferred Taxes Relevant

    NARCIS (Netherlands)

    Brouwer, Arjan; Naarding, Ewout

    2018-01-01

    We analyse the conceptual problems in current accounting for deferred taxes and provide solutions derived from the literature in order to make International Financial Reporting Standards (IFRS) deferred tax numbers value-relevant. In our view, the empirical results concerning the value relevance of

  10. Parsimonious relevance models

    NARCIS (Netherlands)

    Meij, E.; Weerkamp, W.; Balog, K.; de Rijke, M.; Myang, S.-H.; Oard, D.W.; Sebastiani, F.; Chua, T.-S.; Leong, M.-K.

    2008-01-01

    We describe a method for applying parsimonious language models to re-estimate the term probabilities assigned by relevance models. We apply our method to six topic sets from test collections in five different genres. Our parsimonious relevance models (i) improve retrieval effectiveness in terms of

  11. Enactments in Psychoanalysis: Therapeutic Benefits.

    Science.gov (United States)

    Stern, Stanley

    The therapeutic benefits of enactments are addressed. Relevant literature reveals disparate conceptions about the nature and use of enactments. Clarification of the term is discussed. This analyst's theoretical and technical evolution is addressed; it is inextricably related to using enactments. How can it not be? A taxonomy of enactments is presented. The article considers that enactments may be fundamental in the evolution from orthodox to contemporary analytic technique. Assumptions underlying enactments are explored, as are guidelines for using enactments. Finally, the article posits that enactments have widened the scope of analysis and contributed to its vitality.

  12. Mexico City normal weight children exposed to high concentrations of ambient PM2.5 show high blood leptin and endothelin-1, vitamin D deficiency, and food reward hormone dysregulation versus low pollution controls. Relevance for obesity and Alzheimer disease.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; D'Angiulli, Amedeo; Rodríguez-Díaz, Joel; Blaurock-Busch, Eleonore; Busch, Yvette; Chao, Chih-kai; Thompson, Charles; Mukherjee, Partha S; Torres-Jardón, Ricardo; Perry, George

    2015-07-01

    Millions of Mexico, US and across the world children are overweight and obese. Exposure to fossil-fuel combustion sources increases the risk for obesity and diabetes, while long-term exposure to fine particulate matter (PM2.5) and ozone (O3) above US EPA standards is associated with increased risk of Alzheimer's disease (AD). Mexico City Metropolitan Area children are chronically exposed to PM2.5 and O3 concentrations above the standards and exhibit systemic, brain and intrathecal inflammation, cognitive deficits, and Alzheimer disease neuropathology. We investigated adipokines, food reward hormones, endothelial dysfunction, vitamin D and apolipoprotein E (APOE) relationships in 80 healthy, normal weight 11.1±3.2 year olds matched by age, gender, BMI and SES, low (n: 26) versus high (n:54) PM2.5 exposures. Mexico City children had higher leptin and endothelin-1 (pMexico City APOE 4 versus 3 children had higher glucose (p=0.009). Serum 25-hydroxyvitamin DMexico City children. Leptin is strongly positively associated to PM 2.5 cumulative exposures. Residing in a high PM2.5 and O3 environment is associated with 12h fasting hyperleptinemia, altered appetite-regulating peptides, vitamin D deficiency, and increases in ET-1 in clinically healthy children. These changes could signal the future trajectory of urban children towards the development of insulin resistance, obesity, type II diabetes, premature cardiovascular disease, addiction-like behavior, cognitive impairment and Alzheimer's disease. Increased efforts should be made to decrease pediatric PM2.5 exposures, to deliver health interventions prior to the development of obesity and to identify and mitigate environmental factors influencing obesity and Alzheimer disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Possibility of Predicting Serotonin Transporter Occupancy From the In Vitro Inhibition Constant for Serotonin Transporter, the Clinically Relevant Plasma Concentration of Unbound Drugs, and Their Profiles for Substrates of Transporters.

    Science.gov (United States)

    Yahata, Masahiro; Chiba, Koji; Watanabe, Takao; Sugiyama, Yuichi

    2017-09-01

    Accurate prediction of target occupancy facilitates central nervous system drug development. In this review, we discuss the predictability of serotonin transporter (SERT) occupancy in human brain estimated from in vitro K i values for human SERT and plasma concentrations of unbound drug (C u,plasma ), as well as the impact of drug transporters in the blood-brain barrier. First, the geometric means of in vitro K i values were compared with the means of in vivo K i values (K i,u,plasma ) which were calculated as C u,plasma values at 50% occupancy of SERT obtained from previous clinical positron emission tomography/single photon emission computed tomography imaging studies for 6 selective serotonin transporter reuptake inhibitors and 3 serotonin norepinephrine reuptake inhibitors. The in vitro K i values for 7 drugs were comparable to their in vivo K i,u,plasma values within 3-fold difference. SERT occupancy was overestimated for 5 drugs (P-glycoprotein substrates) and underestimated for 2 drugs (presumably uptake transporter substrates, although no evidence exists as yet). In conclusion, prediction of human SERT occupancy from in vitro K i values and C u,plasma was successful for drugs that are not transporter substrates and will become possible in future even for transporter substrates, once the transporter activities will be accurately estimated from in vitro experiments. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  14. Culturally Relevant Cyberbullying Prevention

    OpenAIRE

    Phillips, Gregory John

    2017-01-01

    In this action research study, I, along with a student intervention committee of 14 members, developed a cyberbullying intervention for a large urban high school on the west coast. This high school contained a predominantly African American student population. I aimed to discover culturally relevant cyberbullying prevention strategies for African American students. The intervention committee selected video safety messages featuring African American actors as the most culturally relevant cyber...

  15. [Limitation of the therapeutic effort].

    Science.gov (United States)

    Herreros, B; Palacios, G; Pacho, E

    2012-03-01

    The limitation of the therapeutic effort (LTE) consists in not applying extraordinary or disproportionate measures for therapeutic purposes that are proposed for a patient with poor life prognosis and/or poor quality of life. There are two types. The first is to not initiate certain measures or to withdraw them when they are established. A decision of the LTE should be based on some rigorous criteria, so that we make the following proposal. First, it is necessary to know the most relevant details of the case to make a decision: the preferences of the patient, the preferences of the family when pertinent, the prognosis (severity), the quality of life and distribution of the limited resources. After, the decision should be made. In this phase, participatory deliberation should be established to clarify the end of the intervention. Finally, if it is decided to perform an LTE, it should be decided how to do it. Special procedures, disproportionate measures, that are useless and vain should not be initiated for the therapeutic objective designed (withdraw them if they have been established). When it has been decided to treat a condition (interim measures), the treatment should be maintained. This complex phase may need stratification of he measures. Finally, the necessary palliative measures should be established. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  16. The Limits to Relevance

    Science.gov (United States)

    Averill, M.; Briggle, A.

    2006-12-01

    Science policy and knowledge production lately have taken a pragmatic turn. Funding agencies increasingly are requiring scientists to explain the relevance of their work to society. This stems in part from mounting critiques of the "linear model" of knowledge production in which scientists operating according to their own interests or disciplinary standards are presumed to automatically produce knowledge that is of relevance outside of their narrow communities. Many contend that funded scientific research should be linked more directly to societal goals, which implies a shift in the kind of research that will be funded. While both authors support the concept of useful science, we question the exact meaning of "relevance" and the wisdom of allowing it to control research agendas. We hope to contribute to the conversation by thinking more critically about the meaning and limits of the term "relevance" and the trade-offs implicit in a narrow utilitarian approach. The paper will consider which interests tend to be privileged by an emphasis on relevance and address issues such as whose goals ought to be pursued and why, and who gets to decide. We will consider how relevance, narrowly construed, may actually limit the ultimate utility of scientific research. The paper also will reflect on the worthiness of research goals themselves and their relationship to a broader view of what it means to be human and to live in society. Just as there is more to being human than the pragmatic demands of daily life, there is more at issue with knowledge production than finding the most efficient ways to satisfy consumer preferences or fix near-term policy problems. We will conclude by calling for a balanced approach to funding research that addresses society's most pressing needs but also supports innovative research with less immediately apparent application.

  17. Relevant Subspace Clustering

    DEFF Research Database (Denmark)

    Müller, Emmanuel; Assent, Ira; Günnemann, Stephan

    2009-01-01

    Subspace clustering aims at detecting clusters in any subspace projection of a high dimensional space. As the number of possible subspace projections is exponential in the number of dimensions, the result is often tremendously large. Recent approaches fail to reduce results to relevant subspace...... clusters. Their results are typically highly redundant, i.e. many clusters are detected multiple times in several projections. In this work, we propose a novel model for relevant subspace clustering (RESCU). We present a global optimization which detects the most interesting non-redundant subspace clusters...... achieves top clustering quality while competing approaches show greatly varying performance....

  18. Dental therapeutic systems.

    Science.gov (United States)

    Iqbal, Zeenat; Jain, Nilu; Jain, Gaurav K; Talegaonkar, Sushama; Ahuja, Alka; Khar, Roop K; Ahmad, Farhan J

    2008-01-01

    The recognition of periodontal diseases as amenable to local antibiotherapy has resulted in a paradigmatic shift in treatment modalities of dental afflictions. Moreover the presence of antimicrobial resistance, surfacing of untoward reactions owing to systemic consumption of antibiotics has further advocated the use of local delivery of physiologically active substances into the periodontal pocket. While antimicrobials polymerized into acrylic strips, incorporated into biodegradable collagen and hollow permeable cellulose acetate fibers, multiparticulate systems, bio-absorbable dental materials, biodegradable gels/ointments, injectables, mucoadhesive microcapsules and nanospheres will be more amenable for direct placement into the periodontal pockets the lozenges, buccoadhesive tablets, discs or gels could be effectively used to mitigate the overall gingival inflammation. Whilst effecting controlled local delivery of a few milligram of an antibacterial agent within the gingival crevicular fluid for a longer period of time, maintaining therapeutic concentrations such delivery devices will circumvent all adverse effects to non- oral sites. Since the pioneering efforts of Goodson and Lindhe in 1989, delivery at gingival and subgingival sites has witnessed a considerable progress. The interest in locally active systems is evident from the patents being filed and granted. The present article shall dwell in reviewing the recent approaches being proffered in the field. Patents as by Shefer, et al. US patent, 6589562 dealing with multicomponent biodegradable bioadhesive controlled release system for oral care products, Lee, et al. 2001, US patent 6193994, encompassing a locally administrable, biodegradable and sustained-release pharmaceutical composition for periodontitis and process for preparation thereof and method of treating periodontal disease as suggested by Basara in 2004via US patent 6830757, shall be the types of intellectual property reviewed and presented in

  19. Is Information Still Relevant?

    Science.gov (United States)

    Ma, Lia

    2013-01-01

    Introduction: The term "information" in information science does not share the characteristics of those of a nomenclature: it does not bear a generally accepted definition and it does not serve as the bases and assumptions for research studies. As the data deluge has arrived, is the concept of information still relevant for information…

  20. Tissue Distribution of a Therapeutic Monoclonal Antibody Determined by Large Pore Microdialysis.

    Science.gov (United States)

    Jadhav, Satyawan B; Khaowroongrueng, Vipada; Fueth, Matthias; Otteneder, Michael B; Richter, Wolfgang; Derendorf, Hartmut

    2017-09-01

    Therapeutic monoclonal antibodies (mAbs) exhibit limited distribution to the target tissues. Determination of target tissue interstitial concentration of mAbs is an important aspect in the assessment of their pharmacokinetic/pharmacodynamics relationship especially for mAbs targeting membrane bound receptors. The pharmacokinetics of R7072, a full length mAb (IgG) targeting human insulin-like growth factor-1 receptor was evaluated following a single intravenous dose at 1, 6.25, and 25 mg/kg in healthy female SCID-beige mice. R7072 showed linear pharmacokinetics over the dose range tested and was characterized by low systemic clearance and long terminal half-life. Furthermore, interstitial distribution of R7072 was evaluated in liver, skin, kidney, and muscle tissues using large pore microdialysis (MD) after intravenous administration of 10 mg/kg dose in mice. The relative recoveries of R7072 were consistent and similar between in vitro and in vivo MD experiments. The tissue and interstitial concentrations were significantly lower compared to serum concentrations and found to be highest in liver and lowest in muscle. The interstitial concentrations of R7072 were approximately 2-fold to 4-fold lower than corresponding total tissue concentrations. Large pore MD appears to be an attractive approach for direct measurement of pharmacologically relevant concentrations of therapeutic mAbs in tissue interstitial fluid. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  1. Information Needs/Relevance

    OpenAIRE

    Wildemuth, Barbara M.

    2009-01-01

    A user's interaction with a DL is often initiated as the result of the user experiencing an information need of some kind. Aspects of that experience and how it might affect the user's interactions with the DL are discussed in this module. In addition, users continuously make decisions about and evaluations of the materials retrieved from a DL, relative to their information needs. Relevance judgments, and their relationship to the user's information needs, are discussed in this module. Draft

  2. A Critical Analysis of Concentration and Competition in the Indian Pharmaceutical Market.

    Science.gov (United States)

    Mehta, Aashna; Hasan Farooqui, Habib; Selvaraj, Sakthivel

    2016-01-01

    It can be argued that with several players marketing a large number of brands, the pharmaceutical market in India is competitive. However, the pharmaceutical market should not be studied as a single market but, as a sum total of a large number of individual sub-markets. This paper examines the methodological issues with respect to defining the relevant market involved in studying concentration in the pharmaceutical market in India. Further, we have examined whether the Indian pharmaceutical market is competitive. Indian pharmaceutical market was studied using PharmaTrac, the sales audit data from AIOCD-AWACS, that organises formulations into 5 levels of therapeutic classification based on the EphMRA system. The Herfindahl-Hirschman Index (HHI) was used as the indicator of market concentration. We calculated HHI for the entire pharmaceutical market studied as a single market as well as at the five different levels of therapeutic classification. Whereas the entire pharmaceutical market taken together as a single market displayed low concentration (HHI = 226.63), it was observed that if each formulation is defined as an individual sub-market, about 69 percent of the total market in terms of market value displayed at least moderate concentration. Market should be defined taking into account the ease of substitutability. Since, patients cannot themselves substitute the formulation prescribed by the doctor with another formulation with the same indication and therapeutic effect, owing to information asymmetry, it is appropriate to study market concentration at the narrower levels of therapeutic classification.

  3. Individualised cancer therapeutics: dream or reality? Therapeutics construction.

    Science.gov (United States)

    Shen, Yuqiao; Senzer, Neil; Nemunaitis, John

    2005-11-01

    The analysis of DNA microarray and proteomic data, and the subsequent integration into functional expression sets, provides a circuit map of the hierarchical cellular networks responsible for sustaining the viability and environmental competitiveness of cancer cells, that is, their robust systematics. These technologies can be used to 'snapshot' the unique patterns of molecular derangements and modified interactions in cancer, and allow for strategic selection of therapeutics that best match the individual profile of the tumour. This review highlights technology that can be used to selectively disrupt critical molecular targets and describes possible vehicles to deliver the synthesised molecular therapeutics to the relevant cellular compartments of the malignant cells. RNA interference (RNAi) involves a group of evolutionarily conserved gene silencing mechanisms in which small sequences of double-stranded RNA or intrinsic antisense RNA trigger mRNA cleavage or translational repression, respectively. Although RNAi molecules can be synthesised to 'silence' virtually any gene, even if upregulated, a mechanism for selective delivery of RNAi effectors to sites of malignant disease remains challenging. The authors will discuss gene-modified conditionally replicating viruses as candidate vehicles for the delivery of RNAi.

  4. Therapeutic Drug Monitoring of Lithium

    DEFF Research Database (Denmark)

    Mose, Tina; Damkier, Per; Petersen, Magnus

    2015-01-01

    BACKGROUND: Serum lithium is monitored to ensure levels within the narrow therapeutic window. This study examines the interlaboratory variation and inaccuracy of lithium monitoring in Denmark. METHODS: In 16 samples consisting of (1) control materials (n = 4), (2) pooled patient serum (n = 5......), and (3) serum from individual patients (n = 7), lithium was measured in 19 laboratories using 20 different instruments. The lithium concentrations were targeted by a reference laboratory. Ion-selective electrode (n = 5), reflective spectrophotometric (RSM, n = 5), and spectrophotometric (n = 10) methods...... of >12%. Seven of these instruments had a systematic positive or negative bias and more so at lower lithium concentrations. Three poorly calibrated instruments were found in the ion-selective electrode group, 3 in the spectrophotometric group, and 2 in the RSM group. The instruments using reflectance...

  5. Concentrated Ownership

    DEFF Research Database (Denmark)

    Rose, Caspar

    2014-01-01

    This entry summarizes the main theoretical contributions and empirical findings in relation to concentrated ownership from a law and economics perspective. The various forms of concentrated ownership are described as well as analyzed from the perspective of the legal protection of investors......, especially minority shareholders. Concentrated ownership is associated with benefits and costs. Concentrated ownership may reduce agency costs by increased monitoring of top management. However, concentrated ownership may also provide dominating owners with private benefits of control....

  6. Therapeutical aspect of trichomoniasis

    Directory of Open Access Journals (Sweden)

    Vukićević Jelica

    2003-01-01

    phases proceeding in succession, in so far TV had not been eliminated by previous one. The number of cured patients, according to therapeutical phases, was shown in Table 4. Three patients (1.39 %, 2 males and 1 female were not cured in spite of all three completed phases of therapeutical protocol. In all three cases, TV was eliminated by MND application in dose of 3 g/daily, during two days. The failure of minute MND treatment was analyzed in relation to clinical forms of the infection (manifested or asymptomatic, as well as in relation to types of infection (single- or associated infection. The incidence of refractory trichomoniasis treated by a single metronidazole dose of 2 g was significantly higher in the group of patients with polyinfection (c2=18.270 p<0.01. There was no significant difference of resistance to a single MND dose between the groups with manifested and asymptomatic trichomoniasis (c2=0.321; p<0.01. The prevalence of TV in vaginal and urethral smears indicates the significant incidence of trichomoniasis in STD. TV was more frequently isolated in patients with clinically manifested infection. TV susceptibility to MND was tested in vitro in aerobic and anaerobic conditions. The resistance of strains under in vitro conditions did not correlate with refractory feature of trichomoniasis to MND application [7 17, 18]. The success of trichomoniasis treatment depends upon multiple factors, including: a TV susceptibility to drug, b intravaginal redox potential, c drug concentration in situ, d associated microorganisms that may modify the amount of the drug available in situ [7, 18, 21]. The results of our investigation argue for the latter item, verifying that TV resistance to MND is higher in patients with polyinfection in relation to those with monoinfection (significant difference, c2=18.270; p<0.01. Repeated administration of low metronidazole doses may prolong the therapy of trichomonas infections, while application of high doses (over 3 g/day may result

  7. [Relevant public health enteropathogens].

    Science.gov (United States)

    Riveros, Maribel; Ochoa, Theresa J

    2015-01-01

    Diarrhea remains the third leading cause of death in children under five years, despite recent advances in the management and prevention of this disease. It is caused by multiple pathogens, however, the prevalence of each varies by age group, geographical area and the scenario where cases (community vs hospital) are recorded. The most relevant pathogens in public health are those associated with the highest burden of disease, severity, complications and mortality. In our country, norovirus, Campylobacter and diarrheagenic E. coli are the most prevalent pathogens at the community level in children. In this paper we review the local epidemiology and potential areas of development in five selected pathogens: rotavirus, norovirus, Shiga toxin-producing E. coli (STEC), Shigella and Salmonella. Of these, rotavirus is the most important in the pediatric population and the main agent responsible for child mortality from diarrhea. The introduction of rotavirus vaccination in Peru will have a significant impact on disease burden and mortality from diarrhea. However, surveillance studies are needed to determine the impact of vaccination and changes in the epidemiology of diarrhea in Peru following the introduction of new vaccines, as well as antibiotic resistance surveillance of clinical relevant bacteria.

  8. Biomedical and therapeutic applications of biosurfactants

    OpenAIRE

    Rodrigues, L. R.; Teixeira, J. A.

    2010-01-01

    During the last years, several applications of biosurfactants with medical purposes have been reported. Biosurfactants are considered relevant molecules for applications in combating many diseases and as therapeutic agents due to their antibacterial, antifungal and antiviral activities. Furthermore, their role as anti-adhesive agents against several pathogens illustrate their utility as suitable anti-adhesive coating agents for medical insertional materials leading to a reduction of a large n...

  9. A generic whole body physiologically based pharmacokinetic model for therapeutic proteins in PK-Sim.

    Science.gov (United States)

    Niederalt, Christoph; Kuepfer, Lars; Solodenko, Juri; Eissing, Thomas; Siegmund, Hans-Ulrich; Block, Michael; Willmann, Stefan; Lippert, Jörg

    2018-04-01

    Proteins are an increasingly important class of drugs used as therapeutic as well as diagnostic agents. A generic physiologically based pharmacokinetic (PBPK) model was developed in order to represent at whole body level the fundamental mechanisms driving the distribution and clearance of large molecules like therapeutic proteins. The model was built as an extension of the PK-Sim model for small molecules incorporating (i) the two-pore formalism for drug extravasation from blood plasma to interstitial space, (ii) lymph flow, (iii) endosomal clearance and (iv) protection from endosomal clearance by neonatal Fc receptor (FcRn) mediated recycling as especially relevant for antibodies. For model development and evaluation, PK data was used for compounds with a wide range of solute radii. The model supports the integration of knowledge gained during all development phases of therapeutic proteins, enables translation from pre-clinical species to human and allows predictions of tissue concentration profiles which are of relevance for the analysis of on-target pharmacodynamic effects as well as off-target toxicity. The current implementation of the model replaces the generic protein PBPK model available in PK-Sim since version 4.2 and becomes part of the Open Systems Pharmacology Suite.

  10. Elliptical concentrators.

    Science.gov (United States)

    Garcia-Botella, Angel; Fernandez-Balbuena, Antonio Alvarez; Bernabeu, Eusebio

    2006-10-10

    Nonimaging optics is a field devoted to the design of optical components for applications such as solar concentration or illumination. In this field, many different techniques have been used to produce optical devices, including the use of reflective and refractive components or inverse engineering techniques. However, many of these optical components are based on translational symmetries, rotational symmetries, or free-form surfaces. We study a new family of nonimaging concentrators called elliptical concentrators. This new family of concentrators provides new capabilities and can have different configurations, either homofocal or nonhomofocal. Translational and rotational concentrators can be considered as particular cases of elliptical concentrators.

  11. Other relevant biological papers

    International Nuclear Information System (INIS)

    Shimizu, M.

    1989-01-01

    A considerable number of CRESP-relevant papers concerning deep-sea biology and radioecology have been published. It is the purpose of this study to call attention to them. They fall into three general categories. The first is papers of general interest. They are mentioned only briefly, and include text references to the global bibliography at the end of the volume. The second are papers that are not only mentioned and referenced, but for various reasons are described in abstract form. The last is a list of papers compiled by H.S.J. Roe specifically for this volume. They are listed in bibliographic form, and are also included in the global bibliography at the end of the volume

  12. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  13. Concentration risk

    Directory of Open Access Journals (Sweden)

    Matić Vesna

    2016-01-01

    Full Text Available Concentration risk has been gaining a special dimension in the contemporary financial and economic environment. Financial institutions are exposed to this risk mainly in the field of lending, mostly through their credit activities and concentration of credit portfolios. This refers to the concentration of different exposures within a single risk category (credit risk, market risk, operational risk, liquidity risk.

  14. Marketing therapeutic recreation services.

    Science.gov (United States)

    Thorn, B E

    1984-01-01

    The use of marketing strategies can enhance the delivery of therapeutic recreation services. This article discusses how agencies can adapt marketing techniques and use them to identify potential markets, improve image, evaluate external pressures, and maximize internal strengths. Four variables that can be controlled and manipulated in a proposed marketing plan are product, price, place and promotion.

  15. Therapeutic Recombinant Monoclonal Antibodies

    Science.gov (United States)

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  16. Therapeutic applications of radiopharmaceuticals

    International Nuclear Information System (INIS)

    Baker, W.J.; Datz, F.L.; Beightol, R.W.

    1987-01-01

    Whether a radiopharmaceutical has diagnostic or therapeutic application depends on both the isotope and pharmaceutical used. For diagnostic applications, the isotope should undergo only γ-decay, since usually only γ-radiation is detected by nuclear medicine cameras. The half-life should be just long enough to allow the procedure to be performed. In contrast, the isotope needed for therapeutic purposes should have particulate radiation, such as a β-particle (electron), since these are locally absorbed an increase the local radiation dose. γ-Radiation, which penetrates the tissues, produces less radiation dose than do Β-particles. Several references dealing with radioactive decay, particulate interactions, and diagnostic and therapeutic applications of radiopharmaceuticals are available. Radiopharmaceuticals can legally be used only by physicians who are qualified by specific training in the safe handling of radionuclides. The experience and training of these physicians must be approved by the Nuclear Regulatory Commission or Agreement State Agency authorized to license the use of radiopharmaceuticals. A list of all byproduct material and procedures is available in the Code of Federal Regulations. Of the many radiopharmaceuticals available for diagnostic and therapeutic use, only those commonly used are discussed in this chapter

  17. Target concentration intervention: beyond Y2K.

    Science.gov (United States)

    Holford, N H

    2001-01-01

    Target concentration intervention (TCI) is proposed as an alternative conceptual strategy to therapeutic drug monitoring (TDM). It is argued that the idea of a therapeutic range has limited the interpretation of measured drug concentrations and diminished the anticipated clinical benefit to patients by use of an oversimplified pharmacodynamic model. TCI on the other hand embraces pharmacokinetic and pharmacodynamic concepts and uses the idea of a target effect and associated target concentration to make rational individual dose decisions.

  18. Acute Organophosphate Poisonings: Therapeutic Dilemmas and New Potential Therapeutic Agents

    International Nuclear Information System (INIS)

    Vucinic, S.; Jovanovic, D.; Vucinic, Z.; Todorovic, V.; Segrt, Z.

    2007-01-01

    It has been six decades since synthesis of organophosphates, but this chapter has not yet come to a closure. Toxic effects of organophosphates are well known and the current therapeutic scheme includes supportive therapy and antidotes. There is a dilemma on whether and when to apply gastric lavage and activated charcoal. According to Position Statement (by EAPCCT) it should be applied only if the patient presents within one hour of ingestion, with potentially lethal ingested dose. Atropine, a competitive antagonist of acetylcholine at m-receptors, which antagonizes bronchosecretion and bronchoconstriction, is the corner stone of acute organophosphate poisoning therapy. There were many attempts to find a more efficient drug, including glycopyrrolate which has been used even in clinical trials, but it still can not replace atropine. The only dilemma about atropine usage which still exists, concerns usage of high atropine dose and scheme of application. The most efficient atropinization is achieved with bolus doses of 1-2mg of atropine i.v push, with repeating the dose on each 5 minutes until signs of atropinization are registered. Diazepam, with its GABA stabilizing effect, reduces central nervous system damage and central respiratory weakness. Oximes reactivate phosphorylated acetylcholinesterase, which still has not gone ageing, reducing acetylcholine concentration and cholinergic crisis. These effects are clearly demonstrated in experimental conditions, but the clinical significance of oximes is still unclear and there are still those who question oxime therapy. For those who approve it, oxime dosage, duration of therapy, the choice of oxime for certain OP is still an open issue. We need new, more efficient antidotes, and those that are in use are only the small part of the therapy which could be used. Experimental studies show favorable therapeutic effect of many agents, but none of them has been introduced in standard treatment of OPI poisoning in the last 30

  19. Concentrator Photovoltaics

    CERN Document Server

    Luque, Antonio L

    2007-01-01

    Photovoltaic solar-energy conversion is one of the most promising technologies for generating renewable energy, and conversion of concentrated sunlight can lead to reduced cost for solar electricity. In fact, photovoltaic conversion of concentrated sunlight insures an efficient and cost-effective sustainable power resource. This book gives an overview of all components, e.g. cells, concentrators, modules and systems, for systems of concentrator photovoltaics. The authors report on significant results related to design, technology, and applications, and also cover the fundamental physics and market considerations. Specific contributions include: theory and practice of sunlight concentrators; an overview of concentrator PV activities; a description of concentrator solar cells; design and technology of modules and systems; manufacturing aspects; and a market study.

  20. User perspectives on relevance criteria

    DEFF Research Database (Denmark)

    Maglaughlin, Kelly L.; Sonnenwald, Diane H.

    2002-01-01

    , partially relevant, or not relevant to their information need; and explained their decisions in an interview. Analysis revealed 29 criteria, discussed positively and negatively, that were used by the participants when selecting passages that contributed or detracted from a document's relevance......This study investigates the use of criteria to assess relevant, partially relevant, and not-relevant documents. Study participants identified passages within 20 document representations that they used to make relevance judgments; judged each document representation as a whole to be relevant...... matter, thought catalyst), full text (e.g., audience, novelty, type, possible content, utility), journal/publisher (e.g., novelty, main focus, perceived quality), and personal (e.g., competition, time requirements). Results further indicate that multiple criteria are used when making relevant, partially...

  1. Therapeutic drug monitoring in pregnancy.

    Science.gov (United States)

    Matsui, Doreen M

    2012-10-01

    Therapeutic drug monitoring (TDM) is commonly recommended to optimize drug dosing regimens of various medications. It has been proposed to guide therapy in pregnant women, in whom physiological changes may lead to altered pharmacokinetics resulting in difficulty in predicting the appropriate drug dosage. Ideally, TDM may play a role in enhancing the effectiveness of treatment while minimizing toxicity of both the mother and fetus. Monitoring of drug levels may also be helpful in assessing adherence to prescribed therapy in selected cases. Limitations exist as therapeutic ranges have only been defined for a limited number of drugs and are based on data obtained in nonpregnant patients. TDM has been suggested for anticonvulsants, antidepressants, and antiretroviral drugs, based on pharmacokinetic studies that have shown reduced drug concentrations. However, there is only relatively limited (and sometimes inconsistent) information regarding the clinical impact of these pharmacokinetic changes during pregnancy and the effect of subsequent dose adjustments. Further studies are required to determine whether implementation of TDM during pregnancy improves outcome and is associated with any benefit beyond that achieved by clinical judgment alone. The cost effectiveness of TDM programs during pregnancy also remains to be examined.

  2. Relevance of Programs for Emotionally Disturbed Youth in Other Lands

    Science.gov (United States)

    David, Henry P.

    1970-01-01

    A survey of current trends was conducted in more than 40 countries. Focus was on the organization of services and their relevance for evolving practices in the United States. Apparent was a willingness to experiment with administrative and therapeutic roles. Ideological differences are important determinants of the organization, range, and quality…

  3. Therapeutic drug monitoring of lopinavir/ritonavir in pregnancy.

    LENUS (Irish Health Repository)

    Lambert, J S

    2011-03-01

    The aim of the study was to determine total and unbound lopinavir (LPV) plasma concentrations in HIV-infected pregnant women receiving lopinavir\\/ritonavir (LPV\\/r tablet) undergoing therapeutic drug monitoring (TDM) during pregnancy and postpartum.

  4. PYTHIOSIS: A THERAPEUTIC APPROACH

    Directory of Open Access Journals (Sweden)

    C. M. C. Falcão

    2015-10-01

    Full Text Available Pythiosis, a disease caused by the oomycete Pythium insidiosum, often presents inefficient response to chemotherapy. It is a consensus that, in spite the several therapeutic protocols, a combination of surgery, chemotherapy and immunotherapy should be used. Surgical excision requires the removal of the entire affected area, with a wide margin of safety. The use of antifungal drugs has resulted in variable results, both in vitro and in vivo, and presents low therapeutic efficiency due to differences in the agent characteristics, which differ from true fungi. Immunotherapy is a non-invasive alternative for the treatment of pythiosis, which aims at modifying the immune response of the host, thereby producing an effective response to the agent. Photodynamic therapy has emerged as a promising technique, with good activity against P. insidiosum in vitro and in vivo. However, more studies are necessary to increase the efficiency of the current treatment protocols and consequently improve the cure rates. This paper aims to conduct a review covering the conventional and recent therapeutic methods against P. insidiosum infections

  5. Antibiotic concentrations in intestinal mucosa.

    Science.gov (United States)

    Malmborg, A S

    1985-01-01

    The concentrations in the intestinal mucosa after the initial dose of cefoxitin, piperacillin and clindamycin have been studied. The antibiotics were given at the induction of anesthesia as prophylaxis to patients undergoing elective colorectal surgery. The concentrations of the antibiotics in serum and intestinal mucosa taken during the operation were determined by the microbiological agar diffusion method. Therapeutic concentrations in intestinal mucosa were maintained during the major part of the operation period. The mean mucosa/serum concentration ratios were for cefoxitin 0.4, for piperacillin 0.5 and for clindamycin 1.2.

  6. Inferring relevance in a changing world

    Directory of Open Access Journals (Sweden)

    Robert C Wilson

    2012-01-01

    Full Text Available Reinforcement learning models of human and animal learning usually concentrate on how we learn the relationship between different stimuli or actions and rewards. However, in real world situations stimuli are ill-defined. On the one hand, our immediate environment is extremely multi-dimensional. On the other hand, in every decision-making scenario only a few aspects of the environment are relevant for obtaining reward, while most are irrelevant. Thus a key question is how do we learn these relevant dimensions, that is, how do we learn what to learn about? We investigated this process of representation learning experimentally, using a task in which one stimulus dimension was relevant for determining reward at each point in time. As in real life situations, in our task the relevant dimension can change without warning, adding ever-present uncertainty engendered by a constantly changing environment. We show that human performance on this task is better described by a suboptimal strategy based on selective attention and serial hypothesis testing rather than a normative strategy based on probabilistic inference. From this, we conjecture that the problem of inferring relevance in general scenarios is too computationally demanding for the brain to solve optimally. As a result the brain utilizes approximations, employing these even in simplified scenarios in which optimal representation learning is tractable, such as the one in our experiment.

  7. Concentrating Radioactivity

    Science.gov (United States)

    Herrmann, Richard A.

    1974-01-01

    By concentrating radioactivity contained on luminous dials, a teacher can make a high reading source for classroom experiments on radiation. The preparation of the source and its uses are described. (DT)

  8. Stroke and Therapeutic Hypothermia

    Directory of Open Access Journals (Sweden)

    Ozlem Ozkan Kuscu

    2016-09-01

    Full Text Available Stroke is significant cause of morbidity and mortality caused by disruption of blood flow. Neural injury occurs with two stage; while primary neural injury occurs with disruption of blood flow, after days and hours with metabolic processes secondary injury develops in tissues which is non injured in the first stage. Therefore it is important to prevent and treat the secondary injury as much as preventing and treating the primary neural injury. In this article developing pathophysiological changes after stroke, mechanisms of therapeutic hypothermia, application methods, the factors that determine the effectiveness, side effects and complications were reviewed. [Archives Medical Review Journal 2016; 25(3.000: 351-368

  9. On relevant boundary perturbations of unitary minimal models

    International Nuclear Information System (INIS)

    Recknagel, A.; Roggenkamp, D.; Schomerus, V.

    2000-01-01

    We consider unitary Virasoro minimal models on the disk with Cardy boundary conditions and discuss deformations by certain relevant boundary operators, analogous to tachyon condensation in string theory. Concentrating on the least relevant boundary field, we can perform a perturbative analysis of renormalization group fixed points. We find that the systems always flow towards stable fixed points which admit no further (non-trivial) relevant perturbations. The new conformal boundary conditions are in general given by superpositions of 'pure' Cardy boundary conditions

  10. Pharmacogenetics approach to therapeutics.

    Science.gov (United States)

    Koo, Seok Hwee; Lee, Edmund Jon Deoon

    2006-01-01

    1. Pharmacogenetics refers to the study of genetically controlled variations in drug response. Functional variants caused by single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolising enzymes, transporters, ion channels and drug receptors have been known to be associated with interindividual and interethnic variation in drug response. Genetic variations in these genes play a role in influencing the efficacy and toxicity of medications. 2. Rapid, precise and cost-effective high-throughput technological platforms are essential for performing large-scale mutational analysis of genetic markers involved in the aetiology of variable responses to drug therapy. 3. The application of a pharmacogenetics approach to therapeutics in general clinical practice is still far from being achieved today owing to various constraints, such as limited accessibility of technology, inadequate knowledge, ambiguity of the role of variants and ethical concerns. 4. Drug actions are determined by the interplay of several genes encoding different proteins involved in various biochemical pathways. With rapidly emerging SNP discovery technological platforms and widespread knowledge on the role of SNPs in disease susceptibility and variability in drug response, the pharmacogenetics approach to therapeutics is anticipated to take off in the not-too-distant future. This will present profound clinical, economic and social implications for health care.

  11. Therapeutic nuclear medicine

    International Nuclear Information System (INIS)

    Baum, Richard P.

    2014-01-01

    Discusses all aspects of radionuclide therapy, including basic principles, newly available treatments, regulatory requirements, and future trends. Provides the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Explains the role of the therapeutic nuclear physician in effectively coordinating a diverse multidisciplinary team. Written by leading experts. The recent revolution in molecular biology offers exciting new opportunities for targeted radionuclide therapy. The selective irradiation of tumor cells through molecular biological mechanisms is now permitting the radiopharmaceutical control of tumors that are unresectable and unresponsive to either chemotherapy or conventional radiotherapy. In this up-to-date, comprehensive book, world-renowned experts discuss the basic principles of radionuclide therapy, explore in detail the available treatments, explain the regulatory requirements, and examine likely future developments. The full range of clinical applications is considered, including thyroid cancer, hematological malignancies, brain tumors, liver cancer, bone and joint disease, and neuroendocrine tumors. The combination of theoretical background and practical information will provide the reader with all the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Careful attention is also paid to the important role of the therapeutic nuclear physician in delivering the effective coordination of a diverse multidisciplinary team that is essential to the safe provision of treatment.

  12. Mechanisms of Plasma Therapeutics

    Science.gov (United States)

    Graves, David

    2015-09-01

    In this talk, I address research directed towards biomedical applications of atmospheric pressure plasma such as sterilization, surgery, wound healing and anti-cancer therapy. The field has seen remarkable growth in the last 3-5 years, but the mechanisms responsible for the biomedical effects have remained mysterious. It is known that plasmas readily create reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS (or RONS), in addition to a suite of other radical and non-radical reactive species, are essential actors in an important sub-field of aerobic biology termed ``redox'' (or oxidation-reduction) biology. It is postulated that cold atmospheric plasma (CAP) can trigger a therapeutic shielding response in tissue in part by creating a time- and space-localized, burst-like form of oxy-nitrosative stress on near-surface exposed cells through the flux of plasma-generated RONS. RONS-exposed surface layers of cells communicate to the deeper levels of tissue via a form of the ``bystander effect,'' similar to responses to other forms of cell stress. In this proposed model of CAP therapeutics, the plasma stimulates a cellular survival mechanism through which aerobic organisms shield themselves from infection and other challenges.

  13. Therapeutic nuclear medicine

    Energy Technology Data Exchange (ETDEWEB)

    Baum, Richard P. (ed.) [ENETS Center of Excellence, Bad Berka (Germany). THERANOSTICS Center for Molecular Radiotherapy and Molecular Imaging

    2014-07-01

    Discusses all aspects of radionuclide therapy, including basic principles, newly available treatments, regulatory requirements, and future trends. Provides the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Explains the role of the therapeutic nuclear physician in effectively coordinating a diverse multidisciplinary team. Written by leading experts. The recent revolution in molecular biology offers exciting new opportunities for targeted radionuclide therapy. The selective irradiation of tumor cells through molecular biological mechanisms is now permitting the radiopharmaceutical control of tumors that are unresectable and unresponsive to either chemotherapy or conventional radiotherapy. In this up-to-date, comprehensive book, world-renowned experts discuss the basic principles of radionuclide therapy, explore in detail the available treatments, explain the regulatory requirements, and examine likely future developments. The full range of clinical applications is considered, including thyroid cancer, hematological malignancies, brain tumors, liver cancer, bone and joint disease, and neuroendocrine tumors. The combination of theoretical background and practical information will provide the reader with all the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Careful attention is also paid to the important role of the therapeutic nuclear physician in delivering the effective coordination of a diverse multidisciplinary team that is essential to the safe provision of treatment.

  14. Cure of tuberculosis despite serum concentrations of antituberculosis drugs below published reference ranges.

    Science.gov (United States)

    Meloni, Monica; Corti, Natascia; Müller, Daniel; Henning, Lars; Gutteck, Ursula; von Braun, Amrei; Weber, Rainer; Fehr, Jan

    2015-01-01

    Therapeutic target serum concentrations of first-line antituberculosis drugs have not been well defined in clinical studies in tuberculosis (TB) patients. We retrospectively investigated the estimated maximum serum concentrations (eC max) of antituberculosis drugs and clinical outcome of TB patients with therapeutic drug monitoring performed between 2010-2012 at our institution, and follow-up until March 2014. The eC max was defined as the highest serum concentration during a sampling period (2, 4 and 6 hours after drug ingestion). We compared the results with published eC max values, and categorised them as either "within reference range", "low eC max", or "very low eC max".Low/very low eC max-levels were defined as follows: isoniazid 2-3/max levels were classified as "low" or "very low". The eC max was below the relevant reference range in 80% of isoniazid, 95% of rifampicin, 30% of pyrazinamide, and 30% of ethambutol measurements. All but one patient were cured of tuberculosis. Although many antituberculosis drug serum concentrations were below the widely used reference ranges, 16 of 17 patients were cured of tuberculosis. These results challenge the use of the published reference ranges for therapeutic drug monitoring.

  15. HYPOLIPEMIC THERAPY AND LOW SERUM CHOLESTEROL CONCENTRATION

    Directory of Open Access Journals (Sweden)

    Vladmila Bojanic

    2004-01-01

    Full Text Available Low concentration of plasma lipoproteins (hypolipoproteinemia presents decreasing concentrations of all or particular lipids components. Classification of hypolipoproteinemia (hypoLP divides them into: primary (hereditary and secondary. Primary hipoLP are rare diseases and their main characteristic is disorder of apolipoproteins synthesis, which leads to low serum cholesterol concentration. Secondary hipoLP are presented in many diseases. They have diagnostic, prognostic significance and present good therapeutic marker. However, modern therapeutic approaches for aggressive lipid lowering pointed out many questions about physiological limits for cholesterol lowering. These approaches, also, open many questions about consequences of low serum concentration of total cholesterol and triglicerides.

  16. [Therapeutic education didactic techniques].

    Science.gov (United States)

    Valverde, Maite; Vidal, Mercè; Jansa, Margarida

    2012-10-01

    This article includes an introduction to the role of Therapeutic Education for Diabetes treatment according to the recommendations of the American Diabetes Association (ADA), the Diabetes Education Study Group (DESG) of the "European Association for Study of Diabetes (EASD) and the clinical Practice Guidelines (CPG) of the Spanish Ministry of Health. We analyze theoretical models and the differences between teaching vs. learning as well as current trends (including Internet), that can facilitate meaningful learning of people with diabetes and their families and relatives. We analyze the differences, similarities, advantages and disadvantages of individual and group education. Finally, we describe different educational techniques (metaplan, case method, brainstorming, role playing, games, seminars, autobiography, forums, chats,..) applicable to individual, group or virtual education and its application depending on the learning objective.

  17. Therapeutic drug monitoring of atazanavir/ritonavir in pregnancy.

    LENUS (Irish Health Repository)

    Else, L J

    2014-11-01

    Pregnant women experience physiological changes during pregnancy that can have a significant impact on antiretroviral pharmacokinetics. Ensuring optimal plasma concentrations of antiretrovirals is essential for maternal health and to minimize the risk of vertical transmission. Here we describe atazanavir\\/ritonavir (ATV\\/r) plasma concentrations in a cohort of pregnant women undergoing routine therapeutic drug monitoring (TDM).

  18. Therapeutic Enactment: Integrating Individual and Group Counseling Models for Change

    Science.gov (United States)

    Westwood, Marvin J.; Keats, Patrice A.; Wilensky, Patricia

    2003-01-01

    The purpose of this article is to introduce the reader to a group-based therapy model known as therapeutic enactment. A description of this multimodal change model is provided by outlining the relevant background information, key concepts related to specific change processes, and the differences in this model compared to earlier psychodrama…

  19. [Terbinafine : Relevant drug interactions and their management].

    Science.gov (United States)

    Dürrbeck, A; Nenoff, P

    2016-09-01

    The allylamine terbinafine is the probably most frequently prescribed systemic antifungal agent in Germany for the treatment of dermatomycoses and onychomycoses. According to the German drug law, terbinafine is approved for patients who are 18 years and older; however, this antifungal agent is increasingly used off-label for treatment of onychomycoses and tinea capitis in children. Terbinafine is associated with only a few interactions with other drugs, which is why terbinafine can generally be used without problems in older and multimorbid patients. Nevertheless, some potential interactions of terbinafine with certain drug substances are known, including substances of the group of antidepressants/antipsychotics and some cardiovascular drugs. Decisive for the relevance of interactions is-along with the therapeutic index of the substrate and the possible alternative degradation pathways-the genetically determined type of metabolism. When combining terbinafine with tricyclic antidepressants or selective serotonin reuptake inhibitors and serotonin/noradrenalin reuptake inhibitors, the clinical response and potential side effects must be monitored. Problematic is the use of terbinafine with simultaneous treatment with tamoxifen. The administration of potent CYP2D6 inhibitors leads to a diminished efficacy of tamoxifen because one of its most important active metabolites-endoxifen-is not sufficiently available. Therefore, combination of tamoxifen and terbinafine should be avoided. In conclusion, the number of substances which are able to cause clinically relevant interactions in case of simultaneously administration with terbinafine is clear and should be manageable in the dermatological office with adequate monitoring.

  20. Profiles of Dialogue for Relevance

    Directory of Open Access Journals (Sweden)

    Douglas Walton

    2016-12-01

    Full Text Available This paper uses argument diagrams, argumentation schemes, and some tools from formal argumentation systems developed in artificial intelligence to build a graph-theoretic model of relevance shown to be applicable (with some extensions as a practical method for helping a third party judge issues of relevance or irrelevance of an argument in real examples. Examples used to illustrate how the method works are drawn from disputes about relevance in natural language discourse, including a criminal trial and a parliamentary debate.

  1. [Nuclear transfer and therapeutic cloning].

    Science.gov (United States)

    Xu, Xiao-Ming; Lei, An-Min; Hua, Jin-Lian; Dou, Zhong-Ying

    2005-03-01

    Nuclear transfer and therapeutic cloning have widespread and attractive prospects in animal agriculture and biomedical applications. We reviewed that the quality of oocytes and nuclear reprogramming of somatic donor cells were the main reasons of the common abnormalities in cloned animals and the low efficiency of cloning and showed the problems and outlets in therapeutic cloning, such as some basic problems in nuclear transfer affected clinical applications of therapeutic cloning. Study on isolation and culture of nuclear transfer embryonic stem (ntES) cells and specific differentiation of ntES cells into important functional cells should be emphasized and could enhance the efficiency. Adult stem cells could help to cure some great diseases, but could not replace therapeutic cloning. Ethics also impeded the development of therapeutic cloning. It is necessary to improve many techniques and reinforce the research of some basic theories, then somatic nuclear transfer and therapeutic cloning may apply to agriculture reproduction and benefit to human life better.

  2. Toxicological perspectives of inhaled therapeutics and nanoparticles.

    Science.gov (United States)

    Hayes, Amanda J; Bakand, Shahnaz

    2014-07-01

    The human respiratory system is an important route for the entry of inhaled therapeutics into the body to treat diseases. Inhaled materials may consist of gases, vapours, aerosols and particulates. In all cases, assessing the toxicological effect of inhaled therapeutics has many challenges. This article provides an overview of in vivo and in vitro models for testing the toxicity of inhaled therapeutics and nanoparticles implemented in drug delivery. Traditionally, inhalation toxicity has been performed on test animals to identify the median lethal concentration of airborne materials. Later maximum tolerable concentration denoted by LC0 has been introduced as a more ethically acceptable end point. More recently, in vitro methods have been developed, allowing the direct exposure of airborne material to cultured human target cells on permeable porous membranes at the air-liquid interface. Modifications of current inhalation therapies, new pulmonary medications for respiratory diseases and implementation of the respiratory tract for systemic drug delivery are providing new challenges when conducting well-designed inhalation toxicology studies. In particular, the area of nanoparticles and nanocarriers is of critical toxicological concern. There is a need to develop toxicological test models, which characterise the toxic response and cellular interaction between inhaled particles and the respiratory system.

  3. Molecularly targeted therapeutic radiopharmaceuticals

    International Nuclear Information System (INIS)

    Saw, M.M.

    2007-01-01

    Full text: It is generally agreed that current focus of nuclear medicine development should be on molecular imaging and therapy. Though, the widespread use of the terminology 'molecular imaging' is quite recent, nuclear medicine has used molecular imaging techniques for more than 20 years ago. A variety of radiopharmaceuticals have been introduced for the internal therapy of malignant and inflammatory lesions in nuclear medicine. In the field of bio/medical imaging, nuclear medicine is one of the disciplines which has the privilege of organized and well developed chemistry/ pharmacy section; radio-chemistry/radiopharmacy. Fundamental principles have been developed more than 40 years ago and advanced research is going well into postgenomic era. The genomic revolution and dramatically increased insight in the molecular mechanisms underlying pathology have led to paradigm shift in drug development. Likewise does in the nuclear medicine. Here, the author will present current clinical and pre-clinical therapeutic radiopharmaceuticals based on molecular targets such as membrane-bound receptors, enzymes, nucleic acids, sodium iodide symporter, etc, in correlation with fundamentals of radiopharmacy. (author)

  4. Rethinking Therapeutic Misconception in Biobanking

    DEFF Research Database (Denmark)

    Tupasela, Aaro; Snell, Karoliina; Cañada, Jose

    2017-01-01

    Some authors have noted that in biobank research participants may be guided by what is called therapeutic misconception, whereby participants attribute therapeutic intent to research procedures.This article argues that the notion of therapeutic misconception is increasingly less justified when...... underpinnings for the need to separate research and treatment, and thus the notion of therapeutic misconception in the fi rst place. We call this tension between research and treatment ambivalent research advancement to highlight the difficulties that various actors have in managing such shifts within...

  5. Therapeutic cloning: The ethical limits

    International Nuclear Information System (INIS)

    Whittaker, Peter A.

    2005-01-01

    A brief outline of stem cells, stem cell therapy and therapeutic cloning is given. The position of therapeutic cloning with regard to other embryonic manipulations - IVF-based reproduction, embryonic stem formation from IVF embryos and reproductive cloning - is indicated. The main ethically challenging stages in therapeutic cloning are considered to be the nuclear transfer process including the source of eggs for this and the destruction of an embryo to provide stem cells for therapeutic use. The extremely polarised nature of the debate regarding the status of an early human embryo is noted, and some potential alternative strategies for preparing immunocompatible pluripotent stem cells are indicated

  6. Therapeutic cloning in the mouse

    Science.gov (United States)

    Mombaerts, Peter

    2003-01-01

    Nuclear transfer technology can be applied to produce autologous differentiated cells for therapeutic purposes, a concept termed therapeutic cloning. Countless articles have been published on the ethics and politics of human therapeutic cloning, reflecting the high expectations from this new opportunity for rejuvenation of the aging or diseased body. Yet the research literature on therapeutic cloning, strictly speaking, is comprised of only four articles, all in the mouse. The efficiency of derivation of embryonic stem cell lines via nuclear transfer is remarkably consistent among these reports. However, the efficiency is so low that, in its present form, the concept is unlikely to become widespread in clinical practice. PMID:12949262

  7. Relevance theory: pragmatics and cognition.

    Science.gov (United States)

    Wearing, Catherine J

    2015-01-01

    Relevance Theory is a cognitively oriented theory of pragmatics, i.e., a theory of language use. It builds on the seminal work of H.P. Grice(1) to develop a pragmatic theory which is at once philosophically sensitive and empirically plausible (in both psychological and evolutionary terms). This entry reviews the central commitments and chief contributions of Relevance Theory, including its Gricean commitment to the centrality of intention-reading and inference in communication; the cognitively grounded notion of relevance which provides the mechanism for explaining pragmatic interpretation as an intention-driven, inferential process; and several key applications of the theory (lexical pragmatics, metaphor and irony, procedural meaning). Relevance Theory is an important contribution to our understanding of the pragmatics of communication. © 2014 John Wiley & Sons, Ltd.

  8. Clinical relevance in anesthesia journals

    DEFF Research Database (Denmark)

    Lauritsen, Jakob; Møller, Ann M

    2006-01-01

    The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles.......The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles....

  9. Purinergic Signalling: Therapeutic Developments

    Directory of Open Access Journals (Sweden)

    Geoffrey Burnstock

    2017-09-01

    Full Text Available Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990’s when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson’s disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

  10. Clinical relevance of cimetidine drug interactions.

    Science.gov (United States)

    Shinn, A F

    1992-01-01

    The excellent efficacy and tolerability profiles of H2-antagonists have established these agents as the leading class of antiulcer drugs. Attention has been focused on drug interactions with H2-antagonists as a means of product differentiation and because many patients are receiving multiple drug therapy. The main mechanism of most drug interactions involving cimetidine appears to be inhibition of the hepatic microsomal enzyme cytochrome P450, an effect which may be related to the different structures of H2-antagonists. Ranitidine appears to have less affinity than cimetidine for this system. There have been many published case reports and studies of drug interactions with cimetidine, but many of these have provided pharmacokinetic data only, with little information concerning the clinical significance of these findings. Nevertheless, the coadministration of cimetidine with drugs that have a narrow therapeutic margin (such as theophylline) may potentially result in clinically significant adverse effects. The monitoring of serum concentrations of drugs coadministered with cimetidine may reduce the risk of adverse events but does not abolish the problem. However, for most patients, concomitant administration of cimetidine with drugs possessing a wide therapeutic margin is unlikely to pose a significant problem.

  11. Therapeutic Inertia and Treatment Intensification.

    Science.gov (United States)

    Josiah Willock, Robina; Miller, Joseph B; Mohyi, Michelle; Abuzaanona, Ahmed; Muminovic, Meri; Levy, Phillip D

    2018-01-29

    This review aims to emphasize how therapeutic inertia, the failure of clinicians to intensify treatment when blood pressure rises or remains above therapeutic goals, contributes to suboptimal blood pressure control in hypertensive populations. Studies reveal that the therapeutic inertia is quite common and contributes to suboptimal blood pressure control. Quality improvement programs and standardized approaches to support antihypertensive treatment intensification are ways to combat therapeutic inertia. Furthermore, programs that utilize non-physician medical professionals such as pharmacists and nurses demonstrate promise in mitigating the effects of this important problem. Therapeutic inertia impedes antihypertensive management and requires a broad effort to reduce its effects. There is an ongoing need for renewed focus and research in this area to improve hypertension control.

  12. Exubera. Inhale therapeutic systems.

    Science.gov (United States)

    Bindra, Sanjit; Cefalu, William T

    2002-05-01

    Inhale, in colaboration with Pfizer and Aventis Pharma (formerly Hoechst Marion Roussel; HMR), is developing an insulin formulation utilizing its pulmonary delivery technology for macromolecules for the potential treatment of type I and II diabetes. By July 2001, the phase III program had been completed and the companies had begun to assemble data for MAA and NDA filings; however, it was already clear at this time that additional data might be required for filing. By December 2001, it had been decided that the NDA should include an increased level of controlled, long-term pulmonary safety data in diabetic patients and a major study was planned to be completed in 2002, with the NDA filed thereafter (during 2002). US-05997848 was issued to Inhale Therapeutic Systems in December 1999, and corresponds to WO-09524183, filed in February 1995. Equivalent applications have appeared to date in Australia, Brazil, Canada, China, Czech Republic, Europe, Finland, Hungary, Japan, Norway, New Zealand, Poland and South Africa. This family of applications is specific to pulmonary delivery of insulin. In February 1999, Lehman Brothers gave this inhaled insulin a 60% probability of reaching market, with a possible launch date of 2001. The analysts estimated peak sales at $3 billion in 2011. In May 2000, Aventis predicted that estimated peak sales would be in excess of $1 billion. In February 2000, Merrill Lynch expected product launch in 2002 and predicted that it would be a multibillion-dollar product. Analysts Merril Lynch predicted, in September and November 2000, that the product would be launched by 2002, with sales in that year of e75 million, rising to euro 500 million in 2004. In April 2001, Merrill Lynch predicted that filing for this drug would occur in 2001. Following the report of the potential delay in regulatory filing, issued in July 2001, Deutsche Banc Alex Brown predicted a filing would take place in the fourth quarter of 2002 and launch would take place in the first

  13. Shippingport: A relevant decommissioning project

    International Nuclear Information System (INIS)

    Crimi, F.P.

    1988-01-01

    Because of Shippingport's low electrical power rating (72 MWe), there has been some misunderstanding on the relevancy of the Shippingport Station Decommissioning Project (SSDP) to a modern 1175 MWe commercial pressurized water reactor (PWR) power station. This paper provides a comparison of the major components of the reactor plant of the 72 MWe Shippingport Atomic Power Station and an 1175 MWe nuclear plant and the relevancy of the Shippingport decommissioning as a demonstration project for the nuclear industry. For the purpose of this comparison, Portland General Electric Company's 1175 MWe Trojan Nuclear Plant at Rainier, Oregon, has been used as the reference nuclear power plant. 2 refs., 2 figs., 1 tab

  14. Human Factor in Therapeutic Relationship

    Directory of Open Access Journals (Sweden)

    Ramazan Akdogan

    2011-03-01

    Full Text Available herapeutic relationship is a professional relationship that has been structured based on theoretical props. This relationship is a complicated, wide and unique relationship which develops between two people, where both sides' personality and attitudes inevitably interfere. Therapist-client relationship experienced through transference and counter transference, especially in psychodynamic approaches, is accepted as the main aspect of therapeutic process. However, the approaches without dynamic/deterministic tendency also take therapist-client relationship into account seriously and stress uniqueness of interaction between two people. Being a person and a human naturally sometimes may negatively influence the relationship between the therapist and client and result in a relationship going out of the theoretical frame at times. As effective components of a therapeutic process, the factors that stem from being human include the unique personalities of the therapist and the client, their values and their attitude either made consciously or subconsciously. Literature has shown that the human-related factors are too effective to be denied in therapeutic relationship process. Ethical and theoretical knowledge can be inefficient to prevent the negative effects of these factors in therapeutic process at which point a deep insight and supervision would have a critical role in continuing an acceptable therapeutic relationship. This review is focused on the reflection of some therapeutic factors resulting from being human and development of counter transference onto the therapeutic process.

  15. Lovastatin induces apoptosis of ovarian cancer cells and synergizes with doxorubicin: potential therapeutic relevance

    International Nuclear Information System (INIS)

    Martirosyan, Anna; Clendening, James W; Goard, Carolyn A; Penn, Linda Z

    2010-01-01

    Ovarian carcinoma is a rarely curable disease, for which new treatment options are required. As agents that block HMG-CoA reductase and the mevalonate pathway, the statin family of drugs are used in the treatment of hypercholesterolemia and have been shown to trigger apoptosis in a tumor-specific manner. Recent clinical trials show that the addition of statins to traditional chemotherapeutic strategies can increase efficacy of targeting statin-sensitive tumors. Our goal was to assess statin-induced apoptosis of ovarian cancer cells, either alone or in combination with chemotherapeutics, and then determine these mechanisms of action. The effect of lovastatin on ovarian cancer cell lines was evaluated alone and in combination with cisplatin and doxorubicin using several assays (MTT, TUNEL, fixed PI, PARP cleavage) and synergy determined by evaluating the combination index. The mechanisms of action were evaluated using functional, molecular, and pharmacologic approaches. We demonstrate that lovastatin induces apoptosis of ovarian cancer cells in a p53-independent manner and synergizes with doxorubicin, a chemotherapeutic agent used to treat recurrent cases of ovarian cancer. Lovastatin drives ovarian tumor cell death by two mechanisms: first, by blocking HMG-CoA reductase activity, and second, by sensitizing multi-drug resistant cells to doxorubicin by a novel mevalonate-independent mechanism. This inhibition of drug transport, likely through inhibition of P-glycoprotein, potentiates both DNA damage and tumor cell apoptosis. The results of this research provide pre-clinical data to warrant further evaluation of statins as potential anti-cancer agents to treat ovarian carcinoma. Many statins are inexpensive, off-patent generic drugs that are immediately available for use as anti-cancer agents. We provide evidence that lovastatin triggers apoptosis of ovarian cancer cells as a single agent by a mevalonate-dependent mechanism. Moreover, we also show lovastatin synergizes with doxorubicin, an agent administered for recurrent disease. This synergy occurs by a novel mevalonate-independent mechanism that antagonizes drug resistance, likely by inhibiting P-glycoprotein. These data raise important issues that may impact how statins can best be included in chemotherapy regimens

  16. Social and psychological consequences of not crying : Possible associations with psychopathology and therapeutic relevance

    NARCIS (Netherlands)

    Hesdorffer, D.C.; Vingerhoets, A.J.J.M.; Trimble, M.R.

    2017-01-01

    Emotional crying is hypothesized to serve intra- and interpersonal functions. Intrapersonal functions are assumed to facilitate the capacity to recover from emotional distress, thus promoting well-being. Interpersonal functions are postulated to have a major impact on social functioning. We

  17. Severe Alcoholic Pancreatitis-Associated Acute Lung Injury in Veterans: Risks, Mechanisms, Prediction, and Therapeutic Relevance

    Science.gov (United States)

    2017-10-01

    Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Background: Acute pancreatitis is a painful, potentially life -threatening condition of the...pancreas with an unpredictable course. In this study we hope to identify and propose simple and reliable ways to predict and treat acute...time period of 9/30/2016-9/29/2017. Acute pancreatitis is a painful, potentially life -threatening condition of the pancreas with a typically abrupt

  18. Parasite Cathepsin D-Like Peptidases and Their Relevance as Therapeutic Targets

    Czech Academy of Sciences Publication Activity Database

    Sojka, Daniel; Hartmann, David; Bartošová-Sojková, Pavla; Dvořák, Jan

    2016-01-01

    Roč. 32, č. 9 (2016), s. 708-723 ISSN 1471-4922 R&D Projects: GA ČR GA14-33693S; GA ČR GA13-11043S; GA ČR(CZ) GAP302/11/1481 EU Projects: European Commission(XE) 248642 - SCHISTOSOMA PROTEASE Institutional support: RVO:60077344 ; RVO:68378050 Keywords : aspartic peptidases * cathepsin D * hemoglobinolysis * parasites * vectors Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 6.333, year: 2016

  19. Parasite Cathepsin D-Like Peptidases and Their Relevance as Therapeutic Targets

    Czech Academy of Sciences Publication Activity Database

    Sojka, D.; Hartmann, D.; Bartošová-Sojková, P.; Dvořák, Jan

    2016-01-01

    Roč. 32, č. 9 (2016), s. 708-723 ISSN 1471-4922 R&D Projects: GA ČR GA13-11043S; GA ČR(CZ) GAP302/11/1481 Institutional support: RVO:61388963 Keywords : aspartic peptidases * cathepsin D * hemoglobinolysis * parasites * vectors Subject RIV: CE - Biochemistry Impact factor: 6.333, year: 2016

  20. Frontiers in nano-therapeutics

    CERN Document Server

    Tasnim, Nishat; Sai Krishna, Katla; Kalagara, Sudhakar; Narayan, Mahesh; Noveron, Juan C; Joddar, Binata

    2017-01-01

    This brief highlights recent research advances in the area of nano-therapeutics. Nanotechnology holds immense potential for application in a wide range of biological and engineering applications such as molecular sensors for disease diagnosis, therapeutic agents for the treatment of diseases, a vehicle for delivering therapeutics and imaging agents for theranostic applications, both in-vitro and in-vivo. The brief is grouped into the following sections namely, A) Discrete Nanosystems ; B) Anisotropic Nanoparticles; C) Nano-films/coated/layered and D) Nano-composites.

  1. Therapeutic hypothermia for acute stroke

    DEFF Research Database (Denmark)

    Olsen, Tom Skyhøj; Weber, Uno Jakob; Kammersgaard, Lars Peter

    2003-01-01

    Experimental evidence and clinical experience show that hypothermia protects the brain from damage during ischaemia. There is a growing hope that the prevention of fever in stroke will improve outcome and that hypothermia may be a therapeutic option for the treatment of stroke. Body temperature...... obvious therapeutic potential, hypothermia as a form of neuroprotection for stroke has been investigated in only a few very small studies. Therapeutic hypothermia is feasible in acute stroke but owing to serious side-effects--such as hypotension, cardiac arrhythmia, and pneumonia--it is still thought...

  2. Dramatic lives and relevant becomings

    DEFF Research Database (Denmark)

    Henriksen, Ann-Karina; Miller, Jody

    2012-01-01

    of marginality into positions of relevance. The analysis builds on empirical data from Copenhagen, Denmark, gained through ethnographic fieldwork with the participation of 20 female informants aged 13–22. The theoretical contribution proposes viewing conflicts as multi-linear, multi-causal and non...

  3. Regularization in Matrix Relevance Learning

    NARCIS (Netherlands)

    Schneider, Petra; Bunte, Kerstin; Stiekema, Han; Hammer, Barbara; Villmann, Thomas; Biehl, Michael

    A In this paper, we present a regularization technique to extend recently proposed matrix learning schemes in learning vector quantization (LVQ). These learning algorithms extend the concept of adaptive distance measures in LVQ to the use of relevance matrices. In general, metric learning can

  4. Design Considerations in Therapeutic Exergaming

    OpenAIRE

    Doyle, Julie; Kelly, Daniel; Caulfield, B.

    2011-01-01

    In this paper we discuss the importance of feedback in therapeutic exergaming. It is widely believed that exergaming benefits the patient in terms of encouraging adherence and boosting the patient’s confidence of correct execution and feedback is essential in achieving these. However, feedback and in particular visual feedback, may also have potential negative effects on the quality of the exercise. We describe in this paper a prototype single-sensor therapeutic exergame that we have develope...

  5. Evaluation of therapeutic patient education

    OpenAIRE

    D'Ivernois , Jean-François; Gagnayre , Rémi; Assal , Jean-Philippe; Golay , Alain; Libion , France; Deccache , Alain

    2006-01-01

    9 pages; These guidelines mainly focus on the principles of evaluating Therapeutic Patient Education; Over the past thirty years, therapeutic patient education (TPE) has become an essential part of the treatment of long-term diseases. Evaluations of this new practice are expected, and are sometimes imposed according to protocols and criteria that do not always reflect the complexity of changes taking place within patients and healthcare providers. Sometimes, expected results are not achieved ...

  6. Profiling Prostate Cancer Therapeutic Resistance

    OpenAIRE

    Cameron A. Wade; Natasha Kyprianou

    2018-01-01

    The major challenge in the treatment of patients with advanced lethal prostate cancer is therapeutic resistance to androgen-deprivation therapy (ADT) and chemotherapy. Overriding this resistance requires understanding of the driving mechanisms of the tumor microenvironment, not just the androgen receptor (AR)-signaling cascade, that facilitate therapeutic resistance in order to identify new drug targets. The tumor microenvironment enables key signaling pathways promoting cancer cell survival ...

  7. Ethical considerations of therapeutic hypnosis and children.

    Science.gov (United States)

    Etzrodt, Christine M

    2013-04-01

    Historically, therapeutic hypnosis has been met with skepticism within some fields, although acceptance has expanded in recent decades. Development and application of ethical standards and principles has contributed to increased acceptance of hypnosis with children. The Ethics Code of the American Psychological Association (APA, 2002) and the Code of Conduct of the American Society of Clinical Hypnosis (ASCH, 2000) serve as guides to ethical considerations when treating children. From a developmental and practical perspective, children have limited decision-making capacities, therefore special attention should be paid to their rights and welfare. Important ethical considerations relevant to children and hypnosis have emerged, including competence, supervision, informed consent, confidentiality, and boundaries. Considerations are reviewed from a normal and abnormal child development perspective.

  8. Cell-Specific Aptamers as Emerging Therapeutics

    Directory of Open Access Journals (Sweden)

    Cindy Meyer

    2011-01-01

    Full Text Available Aptamers are short nucleic acids that bind to defined targets with high affinity and specificity. The first aptamers have been selected about two decades ago by an in vitro process named SELEX (systematic evolution of ligands by exponential enrichment. Since then, numerous aptamers with specificities for a variety of targets from small molecules to proteins or even whole cells have been selected. Their applications range from biosensing and diagnostics to therapy and target-oriented drug delivery. More recently, selections using complex targets such as live cells have become feasible. This paper summarizes progress in cell-SELEX techniques and highlights recent developments, particularly in the field of medically relevant aptamers with a focus on therapeutic and drug-delivery applications.

  9. Therapeutic physical exercise in neural injury: friend or foe?

    Science.gov (United States)

    Park, Kanghui; Lee, Seunghoon; Hong, Yunkyung; Park, Sookyoung; Choi, Jeonghyun; Chang, Kyu-Tae; Kim, Joo-Heon; Hong, Yonggeun

    2015-12-01

    [Purpose] The intensity of therapeutic physical exercise is complex and sometimes controversial in patients with neural injuries. This review assessed whether therapeutic physical exercise is beneficial according to the intensity of the physical exercise. [Methods] The authors identified clinically or scientifically relevant articles from PubMed that met the inclusion criteria. [Results] Exercise training can improve body strength and lead to the physiological adaptation of skeletal muscles and the nervous system after neural injuries. Furthermore, neurophysiological and neuropathological studies show differences in the beneficial effects of forced therapeutic exercise in patients with severe or mild neural injuries. Forced exercise alters the distribution of muscle fiber types in patients with neural injuries. Based on several animal studies, forced exercise may promote functional recovery following cerebral ischemia via signaling molecules in ischemic brain regions. [Conclusions] This review describes several types of therapeutic forced exercise and the controversy regarding the therapeutic effects in experimental animals versus humans with neural injuries. This review also provides a therapeutic strategy for physical therapists that grades the intensity of forced exercise according to the level of neural injury.

  10. Extracellular vesicles: fundamentals and clinical relevance

    Directory of Open Access Journals (Sweden)

    Wael Nassar

    2015-01-01

    Full Text Available All types of cells of eukaryotic organisms produce and release small nanovesicles into their extracellular environment. Early studies have described these vesicles as ′garbage bags′ only to remove obsolete cellular molecules. Valadi and colleagues, in 2007, were the first to discover the capability of circulating extracellular vesicles (EVs to horizontally transfer functioning gene information between cells. These extracellular vesicles express components responsible for angiogenesis promotion, stromal remodeling, chemoresistance, genetic exchange, and signaling pathway activation through growth factor/receptor transfer. EVs represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, signaling proteins, and RNAs. They contribute to physiology and pathology, and they have a myriad of potential clinical applications in health and disease. Moreover, vesicles can pass the blood-brain barrier and may perhaps even be considered as naturally occurring liposomes. These cell-derived EVs not only represent a central mediator of the disease microenvironment, but their presence in the peripheral circulation may serve as a surrogate for disease biopsies, enabling real-time diagnosis and disease monitoring. In this review, we′ll be addressing the characteristics of different types of extracellular EVs, as well as their clinical relevance and potential as diagnostic markers, and also define therapeutic options.

  11. The Improved Relevance Voxel Machine

    DEFF Research Database (Denmark)

    Ganz, Melanie; Sabuncu, Mert; Van Leemput, Koen

    The concept of sparse Bayesian learning has received much attention in the machine learning literature as a means of achieving parsimonious representations of features used in regression and classification. It is an important family of algorithms for sparse signal recovery and compressed sensing....... Hence in its current form it is reminiscent of a greedy forward feature selection algorithm. In this report, we aim to solve the problems of the original RVoxM algorithm in the spirit of [7] (FastRVM).We call the new algorithm Improved Relevance Voxel Machine (IRVoxM). Our contributions...... and enables basis selection from overcomplete dictionaries. One of the trailblazers of Bayesian learning is MacKay who already worked on the topic in his PhD thesis in 1992 [1]. Later on Tipping and Bishop developed the concept of sparse Bayesian learning [2, 3] and Tipping published the Relevance Vector...

  12. Familial Resemblance for Serum Metabolite Concentrations

    NARCIS (Netherlands)

    Draisma, H.H.M.; Beekman, M.; Pool, R.; van Ommen, G.J.B; Vaarhorst, A.A.M.; de Craen, A.J.; Willemsen, G.; Slagboom, P.E.; Boomsma, D.I.

    2013-01-01

    Metabolomics is the comprehensive study of metabolites, which are the substrates, intermediate, and end products of cellular metabolism. The heritability of the concentrations of circulating metabolites bears relevance for evaluating their suitability as biomarkers for disease. We report aspects of

  13. A modular platform for targeted RNAi therapeutics.

    Science.gov (United States)

    Kedmi, Ranit; Veiga, Nuphar; Ramishetti, Srinivas; Goldsmith, Meir; Rosenblum, Daniel; Dammes, Niels; Hazan-Halevy, Inbal; Nahary, Limor; Leviatan-Ben-Arye, Shani; Harlev, Michael; Behlke, Mark; Benhar, Itai; Lieberman, Judy; Peer, Dan

    2018-03-01

    Previous studies have identified relevant genes and signalling pathways that are hampered in human disorders as potential candidates for therapeutics. Developing nucleic acid-based tools to manipulate gene expression, such as short interfering RNAs 1-3 (siRNAs), opens up opportunities for personalized medicine. Yet, although major progress has been made in developing siRNA targeted delivery carriers, mainly by utilizing monoclonal antibodies (mAbs) for targeting 4-8 , their clinical translation has not occurred. This is in part because of the massive development and production requirements and the high batch-to-batch variability of current technologies, which rely on chemical conjugation. Here we present a self-assembled modular platform that enables the construction of a theoretically unlimited repertoire of siRNA targeted carriers. The self-assembly of the platform is based on a membrane-anchored lipoprotein that is incorporated into siRNA-loaded lipid nanoparticles that interact with the antibody crystallizable fragment (Fc) domain. We show that a simple switch of eight different mAbs redirects the specific uptake of siRNAs by diverse leukocyte subsets in vivo. The therapeutic potential of the platform is demonstrated in an inflammatory bowel disease model by targeting colon macrophages to reduce inflammatory symptoms, and in a Mantle Cell Lymphoma xenograft model by targeting cancer cells to induce cell death and improve survival. This modular delivery platform represents a milestone in the development of precision medicine.

  14. A modular platform for targeted RNAi therapeutics

    Science.gov (United States)

    Kedmi, Ranit; Veiga, Nuphar; Ramishetti, Srinivas; Goldsmith, Meir; Rosenblum, Daniel; Dammes, Niels; Hazan-Halevy, Inbal; Nahary, Limor; Leviatan-Ben-Arye, Shani; Harlev, Michael; Behlke, Mark; Benhar, Itai; Lieberman, Judy; Peer, Dan

    2018-01-01

    Previous studies have identified relevant genes and signalling pathways that are hampered in human disorders as potential candidates for therapeutics. Developing nucleic acid-based tools to manipulate gene expression, such as short interfering RNAs1-3 (siRNAs), opens up opportunities for personalized medicine. Yet, although major progress has been made in developing siRNA targeted delivery carriers, mainly by utilizing monoclonal antibodies (mAbs) for targeting4-8, their clinical translation has not occurred. This is in part because of the massive development and production requirements and the high batch-to-batch variability of current technologies, which rely on chemical conjugation. Here we present a self-assembled modular platform that enables the construction of a theoretically unlimited repertoire of siRNA targeted carriers. The self-assembly of the platform is based on a membrane-anchored lipoprotein that is incorporated into siRNA-loaded lipid nanoparticles that interact with the antibody crystallizable fragment (Fc) domain. We show that a simple switch of eight different mAbs redirects the specific uptake of siRNAs by diverse leukocyte subsets in vivo. The therapeutic potential of the platform is demonstrated in an inflammatory bowel disease model by targeting colon macrophages to reduce inflammatory symptoms, and in a Mantle Cell Lymphoma xenograft model by targeting cancer cells to induce cell death and improve survival. This modular delivery platform represents a milestone in the development of precision medicine.

  15. Evidence Based Digoxin Therapeutic Monitoring - A Lower and Narrower Therapeutic Range

    Directory of Open Access Journals (Sweden)

    Amine BENLMOUDEN

    2016-06-01

    Full Text Available Cardiac glycosides have been used for congestive heart failure and certain cardiac arrhythmias for more than 200 years. Despite the introduction of a variety of new classes of drugs for the management of heart failure, specifically angiotensin-converting enzyme (ACE inhibitors, b-adrenergic antagonists (bblockers, and the aldosterone antagonist spironolactone, digoxin continues to have an important role in long-term outpatient management. However, a narrow margin exists between therapeutic and toxic doses of digoxin, resulting in a high incidence of digoxin toxicity in clinical practice.A wide variety of placebo-controlled clinical trials have unequivocally shown that treatment with digoxin can improve symptoms, quality of life, and exercise tolerance in patients with mild, moderate, or severe heart failure. The clinical relevance of digoxin therapeutic monitoring is also proved but the SDC (Serum Digoxin Conentrations required for optimal clinical efficacy and acceptable toxicity remains controversial. In the last years, international guidelines recommend 1.2 ng/mL as acceptable high level.In this bibliographic synthesis, we aim to collect pertinent informations from MedLine database about exposure-effect relationship in order to assess the evidence level scientific of new digoxin therapeutic monitoring. 

  16. Strategic characterization of anti-drug antibody responses for the assessment of clinical relevance and impact.

    Science.gov (United States)

    Tatarewicz, Suzanna M; Mytych, Daniel T; Manning, Marta Starcevic; Swanson, Steven J; Moxness, Michael S; Chirmule, Narendra

    2014-06-01

    All therapeutic proteins have the potential to induce anti-drug antibodies (ADA). Clinically relevant ADA can impact efficacy and/or safety of a biological therapeutic. Immunogenicity assessment strategy evaluates binding and neutralizing ADA, and the need for additional characterization (e.g., epitope, titer and so on) is determined using a risk-based approach. The choice of characterization assays depends on the type, application and immunogenicity of the therapeutic. ADA characterization can impact the interpretation of the risk profile of a given therapeutic, and offers insight into opportunities for risk mitigation and management. This article describes common ADA characterization methods. Strategic assessment and characterization of clinically relevant ADA are discussed, in order to support clinical options for safe and effective patient care and disease management.

  17. [Eye contact effects: A therapeutic issue?

    Science.gov (United States)

    Baltazar, M; Conty, L

    2016-12-01

    The perception of a direct gaze - that is, of another individual's gaze directed at the observer that leads to eye contact - is known to influence a wide range of cognitive processes and behaviors. We stress that these effects mainly reflect positive impacts on human cognition and may thus be used as relevant tools for therapeutic purposes. In this review, we aim (1) to provide an exhaustive review of eye contact effects while discussing the limits of the dominant models used to explain these effects, (2) to illustrate the therapeutic potential of eye contact by targeting those pathologies that show both preserved gaze processing and deficits in one or several functions that are targeted by the eye contact effects, and (3) to propose concrete ways in which eye contact could be employed as a therapeutic tool. (1) We regroup the variety of eye contact effects into four categories, including memory effects, activation of prosocial behavior, positive appraisals of self and others and the enhancement of self-awareness. We emphasize that the models proposed to account for these effects have a poor predictive value and that further descriptions of these effects is needed. (2) We then emphasize that people with pathologies that affect memory, social behavior, and self and/or other appraisal, and self-awareness could benefit from eye contact effects. We focus on depression, autism and Alzheimer's disease to illustrate our proposal. To our knowledge, no anomaly of eye contact has been reported in depression. Patients suffering from Alzheimer disease, at the early and moderate stage, have been shown to maintain a normal amount of eye contact with their interlocutor. We take into account that autism is controversial regarding whether gaze processing is preserved or altered. In the first view, individuals are thought to elude or omit gazing at another's eyes while in the second, individuals are considered to not be able to process the gaze of others. We adopt the first stance

  18. Occupation and the relevance of primatology to occupational therapy.

    Science.gov (United States)

    Wood, W

    1993-06-01

    The adaptive functions of occupation during the phylogenetic history of the human species and the ontogenetic development of individual primates re examined through a review of relevant research of wild and captive nonhuman primates. This review suggests that the effectiveness of occupation as a therapeutic medium throughout life span development is fundamentally tied to humankind's phylogenetic history. It is accordingly argued that there is considerable justification to maintain occupational therapy's historical commitment to therapeutic occupation as the profession's primary treatment modality. To support this commitment, questions to guide practice and research are identified that emanate from the primate literature and that are highly germane to the therapeutic process in occupational therapy. These questions address: (a) the relationship between the press of the various environments in which occupational therapists practice and subsequent opportunities availed to patients for engagement in occupation; (b) the relationship between the extent to which patients are or are not empowered to exert real control over their use of time and their eventual development of disabling conditions; and (c) the therapeutic efficacy of occupation as compared with other treatment approaches that are not comparably holistic.

  19. Effect of radioimmunoassay procedures on therapeutic drug monitoring

    International Nuclear Information System (INIS)

    Kampa, I.S.

    1985-01-01

    Methods for the measurement of therapeutic drugs have covered every aspect of analysis from extraction to derivatization. In general, published methods were modified to shorten drug extractions and overall analysis time. The use of different standards, as well as the frequent omission of internal standards, often produced large and clinically unacceptable analytical variations. As a result, physicians would adjust drug dosages according to the physiological response to a standard dose. The introduction of radioimmunoassay techniques for the quantitation of therapeutic drugs have made a significant impact on the clinical chemistry laboratory. The similarities of the various assay methods and the technologists' familiarity with the assay protocols have produced clinically relevant results. Clinical laboratories are now able to frequently analyze a large number of samples with acceptable accuracy and precision. The esoteric test once performed infrequently is today a routine analytical assay often performed STAT. Therapeutic drug monitoring has become a major activity in many clinical laboratories

  20. Personalized therapeutics for levofloxacin: a focus on pharmacokinetic concerns

    Directory of Open Access Journals (Sweden)

    Gao CH

    2014-03-01

    Full Text Available Chu-Han Gao,1 Lu-Shan Yu,2 Su Zeng,2 Yu-Wen Huang,1 Quan Zhou11Department of Pharmacy, the Second Affiliated Hospital, School of Medicine, 2Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of ChinaBackground: Personalized medicine should be encouraged because patients are complex, and this complexity results from biological, medical (eg, demographics, genetics, polypharmacy, and multimorbidities, socioeconomic, and cultural factors. Levofloxacin (LVX is a broad-spectrum fluoroquinolone antibiotic. Awareness of personalized therapeutics for LVX seems to be poor in clinical practice, and is reflected in prescribing patterns. Pharmacokinetic–pharmacodynamic studies have raised concerns about suboptimal patient outcomes with the use of LVX for some Gram-negative infections. Meanwhile, new findings in LVX therapeutics have only been sporadically reported in recent years. Therefore, an updated review on personalized LVX treatment with a focus on pharmacokinetic concerns is necessary.Methods: Relevant literature was identified by performing a PubMed search covering the period from January 1993 to December 2013. We included studies describing dosage adjustment and factors determining LVX pharmacokinetics, or pharmacokinetic–pharmacodynamic studies exploring how best to prevent the emergence of resistance to LVX. The full text of each included article was critically reviewed, and data interpretation was performed.Results: In addition to limiting the use of fluoroquinolones, measures such as reducing the breakpoints for antimicrobial susceptibility testing, choice of high-dose short-course of once-daily LVX regimen, and tailoring LVX dose in special patient populations help to achieve the validated pharmacokinetic–pharmacodynamic target and combat the increasing LVX resistance. Obese individuals with normal renal function cleared LVX

  1. Microdosing: Concept, application and relevance

    Directory of Open Access Journals (Sweden)

    Tushar Tewari

    2010-01-01

    Full Text Available The use of microdose pharmacokinetic studies as an essential tool in drug development is still to catch on. While this approach promises potential cost savings and a quantum leap in efficiencies of the drug development process, major hurdles still need to be overcome before the technique becomes commonplace and part of routine practice. Clear regulations in Europe and the USA have had an enabling effect. The lack of enabling provisions for microdosing studies in Indian regulation, despite low risk and manifest relevance for the local drug development industry, is inconsistent with the country′s aspirations to be among the leaders in pharmaceutical research.

  2. Potential therapeutic applications of biosurfactants.

    Science.gov (United States)

    Gudiña, Eduardo J; Rangarajan, Vivek; Sen, Ramkrishna; Rodrigues, Lígia R

    2013-12-01

    Biosurfactants have recently emerged as promising molecules for their structural novelty, versatility, and diverse properties that are potentially useful for many therapeutic applications. Mainly due to their surface activity, these molecules interact with cell membranes of several organisms and/or with the surrounding environments, and thus can be viewed as potential cancer therapeutics or as constituents of drug delivery systems. Some types of microbial surfactants, such as lipopeptides and glycolipids, have been shown to selectively inhibit the proliferation of cancer cells and to disrupt cell membranes causing their lysis through apoptosis pathways. Moreover, biosurfactants as drug delivery vehicles offer commercially attractive and scientifically novel applications. This review covers the current state-of-the-art in biosurfactant research for therapeutic purposes, providing new directions towards the discovery and development of molecules with novel structures and diverse functions for advanced applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. RNAi Therapeutics in Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Seunghee Cha

    2013-03-01

    Full Text Available Since the discovery of RNA interference (RNAi, excitement has grown over its potential therapeutic uses. Targeting RNAi pathways provides a powerful tool to change biological processes post-transcriptionally in various health conditions such as cancer or autoimmune diseases. Optimum design of shRNA, siRNA, and miRNA enhances stability and specificity of RNAi-based approaches whereas it has to reduce or prevent undesirable immune responses or off-target effects. Recent advances in understanding pathogenesis of autoimmune diseases have allowed application of these tools in vitro as well as in vivo with some degree of success. Further research on the design and delivery of effectors of RNAi pathway and underlying molecular basis of RNAi would warrant practical use of RNAi-based therapeutics in human applications. This review will focus on the approaches used for current therapeutics and their applications in autoimmune diseases, including rheumatoid arthritis and Sjögren’s syndrome.

  4. Conflicts in the therapeutic field

    Directory of Open Access Journals (Sweden)

    Antonino Aprea

    2012-06-01

    Full Text Available How the analytical knowledge that compare human consciousness with that, even more disturbing, moving behind his fifth can be said to be “for peace”? It can be - and this will be the contribution of the proposal - the same tortuous and enigmatic of therapeutic practice, with its hesitations and his impulses, to outline a path crossing and overcoming the conflict? May, finally, peace, in the sense of feasibility of intra-and interpersonal dialectic instead of tearing and hostileconfrontation with oneself and with the other, to be a reference in some crucial pivot of ethical therapeutic work? To these questions the intervention seeks to answer retracing some of the highlights of almost three years of therapeutic work with a young woman and her family.

  5. Reactor-produced therapeutic radioisotopes

    International Nuclear Information System (INIS)

    Knapp, F.F. Jr.

    2002-01-01

    The significant worldwide increase in therapeutic radioisotope applications in nuclear medicine, oncology and interventional cardiology requires the dependable production of sufficient levels of radioisotopes for these applications (Reba, 2000; J. Nucl. Med., 1998; Nuclear News, 1999; Adelstein and Manning, 1994). The issues associated with both accelerator- and reactor-production of therapeutic radioisotopes is important. Clinical applications of therapeutic radioisotopes include the use of both sealed sources and unsealed radiopharmaceutical sources. Targeted radiopharmaceutical agents include those for cancer therapy and palliation of bone pain from metastatic disease, ablation of bone marrow prior to stem cell transplantation, treatment modalities for mono and oligo- and polyarthritis, for cancer therapy (including brachytherapy) and for the inhibition of the hyperplastic response following coronary angioplasty and other interventional procedures (For example, see Volkert and Hoffman, 1999). Sealed sources involve the use of radiolabeled devices for cancer therapy (brachytherapy) and also for the inhibition of the hyperplasia which is often encountered after angioplasty, especially with the exponential increase in the use of coronary stents and stents for the peripheral vasculature and other anatomical applications. Since neutron-rich radioisotopes often decay by beta decay or decay to beta-emitting daughter radioisotopes which serve as the basis for radionuclide generator systems, reactors are expected to play an increasingly important role for the production of a large variety of therapeutic radioisotopes required for these and other developing therapeutic applications. Because of the importance of the availability of reactor-produced radioisotopes for these applications, an understanding of the contribution of neutron spectra for radioisotope production and determination of those cross sections which have not yet been established is important. This

  6. Sub-therapeutic doses of fluvastatin and valsartan are more effective than therapeutic doses in providing beneficial cardiovascular pleiotropic effects in rats: A proof of concept study.

    Science.gov (United States)

    Janić, Miodrag; Lunder, Mojca; France Štiglic, Alenka; Jerin, Aleš; Skitek, Milan; Černe, Darko; Marc, Janja; Drevenšek, Gorazd; Šabovič, Mišo

    2017-12-01

    Statins and sartans can, in therapeutic doses, induce pleiotropic cardiovascular effects. Similar has recently been shown also for sub-therapeutic doses. We thus explored and compared the cardiovascular pleiotropic efficacy of sub-therapeutic vs. therapeutic doses. Wistar rats were randomly divided into 7 groups receiving fluvastatin, valsartan and their combination in sub-therapeutic and therapeutic doses, or saline. After 6weeks, the animals were euthanised, their hearts and thoracic aortas isolated, and blood samples taken. Endothelium-dependent relaxation of the thoracic aortae and ischaemic-reperfusion injury of the isolated hearts were assessed along with the related serum parameters and genes expression. Fluvastatin and valsartan alone or in combination were significantly more effective in sub-therapeutic than therapeutic doses. The sub-therapeutic combination greatly increased thoracic aorta endothelium-dependent relaxation and maximally protected the isolated hearts against ischaemia-reperfusion injury and was thus most effective. Beneficial effects were accompanied by increased levels of nitric oxide (NO) and decreased levels of asymmetric dimethylarginine (ADMA) in the serum (again prominently induced by the sub-therapeutic combination). Furthermore, nitric oxide synthase 3 (NOS3) and endothelin receptor type A (EDNRA) genes expression increased, but only in both combination groups and without significant differences between them. In the therapeutic dose groups, fluvastatin and valsartan decreased cholesterol values and systolic blood pressure. Sub-therapeutic doses of fluvastatin and valsartan are more effective in expressing cardiovascular pleiotropic effects than therapeutic doses of fluvastatin and/or valsartan. These results could be of significant clinical relevance. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. [Therapeutic touch and anorexia nervosa].

    Science.gov (United States)

    Satori, Nadine

    2016-01-01

    An innovative practice, therapeutic touch has been used for around ten years in the treatment of eating disorders. Delivered by nurse clinicians having received specific training, this approach is based on nursing diagnoses which identify the major symptoms of this pathology. The support is built around the body and its perceptions. Through the helping relationship, it mobilises the patient's resources to favour a relationship of trust, a letting-go, physical, psychological and emotional relaxation, and improves the therapeutic alliance. Copyright © 2016. Published by Elsevier Masson SAS.

  8. Other relevant numerical modelling papers

    International Nuclear Information System (INIS)

    Chartier, M.

    1989-01-01

    The ocean modelling is a rapidly evolving science and a large number of results have been published. Several categories of papers are of particular interest for this review: the papers published by the international atomic institutions, such as the NEA (for the CRESP or Subseabed Programs), the IAEA (for example the Safety Series, the Technical Report Series or the TECDOC), and the ICRP, and the papers concerned by more fundamental research, which are published in specific scientific literature. This paper aims to list some of the most relevant publications for the CRESP purposes. It means by no way to be exhaustive, but informative on the incontestable progress recently achieved in that field. One should note that some of these papers are so recent that their final version has not yet been published

  9. Industrial relevance of thermophilic Archaea.

    Science.gov (United States)

    Egorova, Ksenia; Antranikian, Garabed

    2005-12-01

    The dramatic increase of newly isolated extremophilic microorganisms, analysis of their genomes and investigations of their enzymes by academic and industrial laboratories demonstrate the great potential of extremophiles in industrial (white) biotechnology. Enzymes derived from extremophiles (extremozymes) are superior to the traditional catalysts because they can perform industrial processes even under harsh conditions, under which conventional proteins are completely denatured. In particular, enzymes from thermophilic and hyperthermophilic Archaea have industrial relevance. Despite intensive investigations, our knowledge of the structure-function relationships of their enzymes is still limited. Information concerning the molecular properties of their enzymes and genes has to be obtained to be able to understand the mechanisms that are responsible for catalytic activity and stability at the boiling point of water.

  10. The Relevance of Hegel's Logic

    Directory of Open Access Journals (Sweden)

    John W Burbidge

    2007-12-01

    Full Text Available Hegel defines his Logic as the science that thinks about thinking.nbsp; But when we interpret that work as outlining what happens when we reason we are vulnerable to Fregersquo;s charge of psychologism.nbsp; I use Hegelrsquo;s tripartite distinction among understanding, dialectical and speculative reason as operations of pure thought to suggest how thinking can work with objective concepts.nbsp; In the last analysis, however, our ability to move from the subjective contingency of representations and ideas to the pure concepts we think develops from mechanical memory, which separates sign from sense so hat we can focus simply on the latter.nbsp; By becoming aware of the connections that underlie our thinking processes we may be able to both move beyond the abstractions of symbolic logic and clarify what informal logicians call relevance.

  11. Therapy Talk: Analyzing Therapeutic Discourse

    Science.gov (United States)

    Leahy, Margaret M.

    2004-01-01

    Therapeutic discourse is the talk-in-interaction that represents the social practice between clinician and client. This article invites speech-language pathologists to apply their knowledge of language to analyzing therapy talk and to learn how talking practices shape clinical roles and identities. A range of qualitative research approaches,…

  12. Therapeutic approaches to genetic disorders

    African Journals Online (AJOL)

    salah

    Although prevention is the ideal goal for genetic disorders, various types of therapeutic ... The patient being ... pirical or aimed at controlling or mediating signs and symptoms without care. ... plications and gene therapy approaches .... genes family, have opened a wide and .... cancer where nanoparticles are used to.

  13. Medical therapeutic effect of hyperthyroidism

    International Nuclear Information System (INIS)

    Lee, K.B.

    1980-01-01

    In order to compare the therapeutic effect as well as side effects between antithyroid therapy and radioiodine therapy in hyperthyroidism, the author evaluated 111 cases of hyperthyroidism which were composed of 57 patients with antithyroid treatment, 23 patients with combined treatment comprising of antithyroid and radioactive iodine ( 131 I) and 31 patients with treatment of 131 I alone. (author)

  14. Patient-relevant treatment goals in psoriasis.

    Science.gov (United States)

    Blome, Christine; Gosau, Ramona; Radtke, Marc A; Reich, Kristian; Rustenbach, Stephan J; Spehr, Christina; Thaçi, Diamant; Augustin, Matthias

    2016-03-01

    Patient-oriented care requires therapeutic decisions to agree with the patients' treatment needs and goals. This study addressed the following questions: What is important to psoriasis patients starting systemic treatment? How stable are these preferences within the first year of treatment? Are treatment goals associated with age, gender, or treatment success? The importance of treatment goals was assessed for patients with moderate-to-severe psoriasis in the German Psoriasis Registry (PsoBest) at baseline (onset of a systemic treatment; n = 3066) and at a 1-year follow-up (n = 1444) using the Patient Benefit Index (PBI). Treatment success was measured with PBI global score and Psoriasis Area Severity Index (PASI). Patients with moderate-to-severe psoriasis pursued a wide range of different goals. The most general treatment goals were rated most relevant, including skin healing and quick skin improvement (94.8/94.5 % "quite" or "very" important), confidence in the therapy (93.0 %), control over the disease (92.3 %), and a clear diagnosis and therapy (89.6 %). Further important goals related to not being in fear of the disease getting worse (84.8 %), reduction in itching (83.9 %), burning (70.6 %), and pain (60.6 %) as well as attaining a normal everyday life (78.4 %) and low treatment burden (64.2-77.9 %). Goals were mostly not associated with sex and gender. Goal importance slightly increased with treatment success. In a substantial proportion of patients (30.3-54.7 %) goal importance changed within 1 year after onset of systemic treatment. We conclude that treatment goal importance should be assessed in clinical practice on a regular basis.

  15. Blocking Avoidance and Escape Responses: Relations With Clinically Relevant Behaviors

    Directory of Open Access Journals (Sweden)

    Juliana Maria Bubna Popovitz

    Full Text Available Abstract: The current study aims to evaluate the possible effects of interrupting problematic clinically relevant behaviors on the percentage of these responses and of clinical improvement-related responses. Two clients were treated with Functional Analytic Psychotherapy (FAP, alternating two conditions (ABAB. On condition A, procedures to the therapist consisted of responding to the clinical improvement responses, and to description of outside of therapeutic setting behaviors, but therapists were advised to ignore problem behaviors emitted in session. During condition B, therapists followed the same procedures, but they were oriented to block (interrupt problematic responses emitted in session. Results suggest increase in the percentage of problem behaviors during condition B. Results are discussed, highlighting the viability of planning the contingent response the therapist emits to clinically relevant behaviors.

  16. Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance.

    Science.gov (United States)

    Dinis-Oliveira, Ricardo Jorge

    2017-02-01

    Psilocybin and psilocin are controlled substances in many countries. These are the two main hallucinogenic compounds of the "magic mushrooms" and both act as agonists or partial agonists at 5-hydroxytryptamine (5-HT) 2A subtype receptors. During the last few years, psilocybin and psilocin have gained therapeutic relevance but considerable physiological variability between individuals that can influence dose-response and toxicological profile has been reported. This review aims to discuss metabolism of psilocybin and psilocin, by presenting all major and minor psychoactive metabolites. Psilocybin is primarily a pro-drug that is dephosphorylated by alkaline phosphatase to active metabolite psilocin. This last is then further metabolized, psilocin-O-glucuronide being the main urinary metabolite with clinical and forensic relevance in diagnosis.

  17. Colonic gas explosion during therapeutic colonoscopy with electrocautery

    Science.gov (United States)

    Ladas, Spiros D; Karamanolis, George; Ben-Soussan, Emmanuel

    2007-01-01

    Therapeutic colonoscopy with electrocautery is widely used around the world. Adequate colonic cleansing is considered a crucial factor for the safety of this procedure. Colonic gas explosion, although rare, is one of the most frightening iatrogenic complications during colonoscopy with electrocautery. This complication is the result of an accumulation of colonic gases to explosive concentrations, but may be prevented by meticulous bowel preparation. The purpose of this review is to discuss the indications and the types of bowel preparations for therapeutic colonoscopy, and to contribute recommendations for the adequate bowel preparation for colonoscopy with electrocautery. PMID:17879396

  18. Garlic: a review of potential therapeutic effects

    Science.gov (United States)

    Bayan, Leyla; Koulivand, Peir Hossain; Gorji, Ali

    2014-01-01

    Throughout history, many different cultures have recognized the potential use of garlic for prevention and treatment of different diseases. Recent studies support the effects of garlic and its extracts in a wide range of applications. These studies raised the possibility of revival of garlic therapeutic values in different diseases. Different compounds in garlic are thought to reduce the risk for cardiovascular diseases, have anti-tumor and anti-microbial effects, and show benefit on high blood glucose concentration. However, the exact mechanism of all ingredients and their long-term effects are not fully understood. Further studies are needed to elucidate the pathophysiological mechanisms of action of garlic as well as its efficacy and safety in treatment of various diseases. PMID:25050296

  19. Therapeutic drug monitoring of atypical antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Grundmann Milan

    2014-12-01

    Full Text Available Schizophrenia is a severe psychiatric disorder often associated with cognitive impairment and affective, mainly depressive, symptoms. Antipsychotic medication is the primary intervention for stabilization of acute psychotic episodes and prevention of recurrences and relapses in patients with schizophrenia. Typical antipsychotics, the older class of antipsychotic agents, are currently used much less frequently than newer atypical antipsychotics. Therapeutic drug monitoring (TDM of antipsychotic drugs is the specific method of clinical pharmacology, which involves measurement of drug serum concentrations followed by interpretation and good cooperation with the clinician. TDM is a powerful tool that allows tailor-made treatment for the specific needs of individual patients. It can help in monitoring adherence, dose adjustment, minimizing the risk of toxicity and in cost-effectiveness in the treatment of psychiatric disorders. The review provides complex knowledge indispensable to clinical pharmacologists, pharmacists and clinicians for interpretation of TDM results.

  20. Limited-Sampling Strategies for Therapeutic Drug Monitoring of Moxifloxacin in Patients With Tuberculosis

    NARCIS (Netherlands)

    Pranger, Arianna D.; Kosterink, Jos G. W.; van Altena, Richard; Aarnoutse, Rob E.; van der Werf, Tjip S.; Uges, Donald R. A.; Alffenaar, Jan-Willem C.

    Background: Moxifloxacin (MFX) is a potent drug for multidrug resistant tuberculosis(TB) treatment and is also useful if first-line agents are not tolerated. Therapeutic drug monitoring may help to prevent treatment failure. Obtaining a full concentration-time curve of MFX for therapeutic drug

  1. Limited-sampling strategies for therapeutic drug monitoring of moxifloxacin in patients with tuberculosis

    NARCIS (Netherlands)

    Pranger, A.D.; Kosterink, J.G.W.; Altena, R. van; Aarnoutse, R.E.; Werf, T.S. van der; Uges, D.R.A.; Alffenaar, J.W.C.

    2011-01-01

    BACKGROUND: Moxifloxacin (MFX) is a potent drug for multidrug resistant tuberculosis(TB) treatment and is also useful if first-line agents are not tolerated. Therapeutic drug monitoring may help to prevent treatment failure. Obtaining a full concentration-time curve of MFX for therapeutic drug

  2. The relevance of "non-relevant metabolites" from plant protection products (PPPs) for drinking water: the German view.

    Science.gov (United States)

    Dieter, Hermann H

    2010-03-01

    evaluation of a "non-relevant metabolite", its HRIV is either set as 1.0 microg/l (HRIV(a)) or as 3.0 microg/l (HRIV(b)) for lifelong exposure. In case a HRIV would be exceeded, UBA recommends to keep on a precautionary action value (PAV) of 10 microg/l for each "non-relevant metabolite". The HRIV(b) is similar to the maximal value derived by application of the TTC-concept for Cramer Class III (4.5 microg/l). The HRIV(a) and the PAV are similar to values in the EU-guidance document for assessing "non-relevant metabolites" in ground water, with the important difference that the drinking water PAV is not intended to be tolerated for permanent exposure. Drinking water containing "non-relevant metabolites" below the respective HRIVs can also be considered as being sufficiently protective against toxicologically relevant oxidative transformation products which may be formed from "non-relevant metabolites" during drinking water treatment with ozone. However, even drinking water where one or several "non-relevant metabolites" are detected above substance-specific HRIVs is suited for human consumption without health risks. Only in special cases (relatively high "non-relevant metabolite" - concentrations), it could be indicated to examine the finished water for transformation products after treatment with ozone if there are no further treatment steps to eliminate or degrade polar compounds. UBA's "non-relevant metabolite-Recommendation" from April 2008 was positively picked up in 2009 by four important stakeholders in the domain of drinking water management as part of a voluntary cooperation agreement. The aim of such cooperation is to limit the transport of "non-relevant metabolites" into the drinking water to the functionally (and agriculturally) unavoidable extent and insofar to meet special precautionary demands. (c) 2009 Elsevier Inc. All rights reserved.

  3. Vygotsky's Crisis: Argument, context, relevance.

    Science.gov (United States)

    Hyman, Ludmila

    2012-06-01

    Vygotsky's The Historical Significance of the Crisis in Psychology (1926-1927) is an important text in the history and philosophy of psychology that has only become available to scholars in 1982 in Russian, and in 1997 in English. The goal of this paper is to introduce Vygotsky's conception of psychology to a wider audience. I argue that Vygotsky's argument about the "crisis" in psychology and its resolution can be fully understood only in the context of his social and political thinking. Vygotsky shared the enthusiasm, widespread among Russian leftist intelligentsia in the 1920s, that Soviet society had launched an unprecedented social experiment: The socialist revolution opened the way for establishing social conditions that would let the individual flourish. For Vygotsky, this meant that "a new man" of the future would become "the first and only species in biology that would create itself." He envisioned psychology as a science that would serve this humanist teleology. I propose that The Crisis is relevant today insofar as it helps us define a fundamental problem: How can we systematically account for the development of knowledge in psychology? I evaluate how Vygotsky addresses this problem as a historian of the crisis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Relevance of equilibrium in multifragmentation

    International Nuclear Information System (INIS)

    Furuta, Takuya; Ono, Akira

    2009-01-01

    The relevance of equilibrium in a multifragmentation reaction of very central 40 Ca + 40 Ca collisions at 35 MeV/nucleon is investigated by using simulations of antisymmetrized molecular dynamics (AMD). Two types of ensembles are compared. One is the reaction ensemble of the states at each reaction time t in collision events simulated by AMD, and the other is the equilibrium ensemble prepared by solving the AMD equation of motion for a many-nucleon system confined in a container for a long time. The comparison of the ensembles is performed for the fragment charge distribution and the excitation energies. Our calculations show that there exists an equilibrium ensemble that well reproduces the reaction ensemble at each reaction time t for the investigated period 80≤t≤300 fm/c. However, there are some other observables that show discrepancies between the reaction and equilibrium ensembles. These may be interpreted as dynamical effects in the reaction. The usual static equilibrium at each instant is not realized since any equilibrium ensemble with the same volume as that of the reaction system cannot reproduce the fragment observables

  5. The effect of immunomodulators on the immunogenicity of TNF-blocking therapeutic monoclonal antibodies: a review

    NARCIS (Netherlands)

    Krieckaert, C.L.; Bartelds, G.M.; Lems, W.F.; Wolbink, G.J.

    2010-01-01

    Therapeutic monoclonal antibodies have revolutionized the treatment of various inflammatory diseases. Immunogenicity against these antibodies has been shown to be clinically important: it is associated with shorter response duration because of diminishing concentrations in the blood and with

  6. Design of multimodal degradable hydrogels for controlled therapeutic delivery

    Science.gov (United States)

    Kharkar, Prathamesh Madhav

    Hydrogels are of growing interest for the delivery of therapeutics to specific sites in the body. For localized drug delivery, hydrophilic polymeric precursors often are laden with bioactive moieties and then directly injected to the site of interest for in situ gel formation. The release of physically entrapped cargo is dictated by Fickian diffusion, degradation of the drug carrier, or a combination of both. The goal of this work was to design and characterize degradable hydrogel formulations that are responsive to multiple biologically relevant stimuli for degradation-mediated delivery of cargo molecules such as therapeutic proteins, growth factors, and immunomodulatory agents. We began by demonstrating the use of cleavable click linkages formed by Michael-type addition reactions in conjunction with hydrolytically cleavable functionalities for the degradation of injectable hydrogels by endogenous stimuli for controlled protein release. Specifically, the reaction between maleimides and thiols was utilized for hydrogel formation, where thiol selection dictates the degradability of the resulting linkage under thiol-rich reducing conditions. Relevant microenvironments where degradation would occur in vivo include those rich in glutathione (GSH), a tripeptide that is found at elevated concentrations in carcinoma tissues. Degradation of the hydrogels was monitored with rheometry and volumetric swelling measurements. Arylthiol-based thioether succinimide linkages underwent degradation via click cleavage and thiol exchange reaction in the presence of GSH and via ester hydrolysis, whereas alkylthiol-based thioether succinimide linkages only undergo degradation by only ester hydrolysis. The resulting control over the degradation rate within a reducing microenvironment resulted in 2.5 fold differences in the release profile of the model protein, a fluorescently-labeled bovine serum albumin, from dually degradable hydrogels compared to non-degradable hydrogels, where the

  7. Conversational evidence in therapeutic dialogue.

    Science.gov (United States)

    Strong, Tom; Busch, Robbie; Couture, Shari

    2008-07-01

    Family therapists' participation in therapeutic dialogue with clients is typically informed by evidence of how such dialogue is developing. In this article, we propose that conversational evidence, the kind that can be empirically analyzed using discourse analyses, be considered a contribution to widening psychotherapy's evidence base. After some preliminaries about what we mean by conversational evidence, we provide a genealogy of evaluative practice in psychotherapy, and examine qualitative evaluation methods for their theoretical compatibilities with social constructionist approaches to family therapy. We then move on to examine the notion of accomplishment in therapeutic dialogue given how such accomplishments can be evaluated using conversation analysis. We conclude by considering a number of research and pedagogical implications we associate with conversational evidence.

  8. [Therapeutic use of cannabis derivatives].

    Science.gov (United States)

    Benyamina, Amine; Reynaud, Michel

    2014-02-01

    The therapeutic use of cannabis has generated a lot of interest in the past years, leading to a better understanding of its mechanisms of action. Countries like the United States and Canada have modified their laws in order to make cannabinoid use legal in the medical context. It's also the case in France now, where a recent decree was issued, authorizing the prescription of medication containing "therapeutic cannabis" (decree no. 2013-473, June 5, 2013). Cannabinoids such as dronabinol, Sativex and nabilone have been tested for the treatment of acute and chronic pain. These agents are most promising to relieve chronic pain associated with cancer, with human immunodeficiency virus infection and with multiple sclerosis. However, longer-term studies are required to determine potential long-term adverse effects and risks of misuse and addiction.

  9. Therapeutic Dancing for Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Lorenna Pryscia Carvalho Aguiar

    2016-06-01

    Full Text Available Therapeutic dancing has been advocated as an effective adjunct to conventional physical therapies for people living with Parkinson's disease (PD. This systematic review evaluates studies on the outcomes of different dance genres on mobility and quality of life in PD. We searched databases including CINHAL (1982–2015, Medline (1922–2015, Scopus (1996–2015, Web of Science (2002–2015, Embase (2007–2015, PEDro (1999–2015 and the Cochrane Library (1996–2015. The key words were: Parkinson's disease, Parkinson*, Parkinsonism, dance, dance therapy, dance genres, safety, feasibility, and quality of life. Two independent investigators reviewed the texts. Only randomized controlled trials, quasirandomized controlled trials, and case series studies were included. There was emerging evidence that therapeutic dance can be safe and feasible for people with mild to moderately severe PD, with beneficial effects on walking, freezing of gait, and health related quality of life.

  10. Therapeutic approaches for celiac disease

    Science.gov (United States)

    Plugis, Nicholas M.; Khosla, Chaitan

    2015-01-01

    Celiac disease is a common, lifelong autoimmune disorder for which dietary control is the only accepted form of therapy. A strict gluten-free diet is burdensome to patients and can be limited in efficacy, indicating there is an unmet need for novel therapeutic approaches to supplement or supplant dietary therapy. Many molecular events required for disease pathogenesis have been recently characterized and inspire most current and emerging drug-discovery efforts. Genome-wide association studies (GWAS) confirm the importance of human leukocyte antigen genes in our pathogenic model and identify a number of new risk loci in this complex disease. Here, we review the status of both emerging and potential therapeutic strategies in the context of disease pathophysiology. We conclude with a discussion of how genes identified during GWAS and follow-up studies that enhance susceptibility may offer insight into developing novel therapies. PMID:26060114

  11. Sinigrin and Its Therapeutic Benefits

    Directory of Open Access Journals (Sweden)

    Anisha Mazumder

    2016-03-01

    Full Text Available Sinigrin (allyl-glucosinolate or 2-propenyl-glucosinolate is a natural aliphatic glucosinolate present in plants of the Brassicaceae family, such as broccoli and brussels sprouts, and the seeds of Brassica nigra (mustard seeds which contain high amounts of sinigrin. Since ancient times, mustard has been used by mankind for its culinary, as well as medicinal, properties. It has been systematically described and evaluated in the classical Ayurvedic texts. Studies conducted on the pharmacological activities of sinigrin have revealed anti-cancer, antibacterial, antifungal, antioxidant, anti-inflammatory, wound healing properties and biofumigation. This current review will bring concise information about the known therapeutic activities of sinigrin. However, the information on known biological activities is very limited and, hence, further studies still need to be conducted and its molecular mechanisms also need to be explored. This review on the therapeutic benefits of sinigrin can summarize current knowledge about this unique phytocompounds.

  12. Personalized therapeutics for levofloxacin: a focus on pharmacokinetic concerns.

    Science.gov (United States)

    Gao, Chu-Han; Yu, Lu-Shan; Zeng, Su; Huang, Yu-Wen; Zhou, Quan

    2014-01-01

    Personalized medicine should be encouraged because patients are complex, and this complexity results from biological, medical (eg, demographics, genetics, polypharmacy, and multimorbidities), socioeconomic, and cultural factors. Levofloxacin (LVX) is a broad-spectrum fluoroquinolone antibiotic. Awareness of personalized therapeutics for LVX seems to be poor in clinical practice, and is reflected in prescribing patterns. Pharmacokinetic-pharmacodynamic studies have raised concerns about suboptimal patient outcomes with the use of LVX for some Gram-negative infections. Meanwhile, new findings in LVX therapeutics have only been sporadically reported in recent years. Therefore, an updated review on personalized LVX treatment with a focus on pharmacokinetic concerns is necessary. Relevant literature was identified by performing a PubMed search covering the period from January 1993 to December 2013. We included studies describing dosage adjustment and factors determining LVX pharmacokinetics, or pharmacokinetic-pharmacodynamic studies exploring how best to prevent the emergence of resistance to LVX. The full text of each included article was critically reviewed, and data interpretation was performed. In addition to limiting the use of fluoroquinolones, measures such as reducing the breakpoints for antimicrobial susceptibility testing, choice of high-dose short-course of once-daily LVX regimen, and tailoring LVX dose in special patient populations help to achieve the validated pharmacokinetic-pharmacodynamic target and combat the increasing LVX resistance. Obese individuals with normal renal function cleared LVX more efficiently than normal-weight individuals. Compared with the scenario in healthy subjects, standard 2-hour spacing of calcium formulations and oral LVX was insufficient to prevent a chelation interaction in cystic fibrosis patients. Inconsistent conclusions were derived from studies of the influence of sex on the pharmacokinetics of LVX, which might be

  13. Potential Therapeutic Effects of Psilocybin.

    Science.gov (United States)

    Johnson, Matthew W; Griffiths, Roland R

    2017-07-01

    Psilocybin and other 5-hydroxytryptamine 2A agonist classic psychedelics have been used for centuries as sacraments within indigenous cultures. In the mid-twentieth century they were a focus within psychiatry as both probes of brain function and experimental therapeutics. By the late 1960s and early 1970s these scientific inquires fell out of favor because classic psychedelics were being used outside of medical research and in association with the emerging counter culture. However, in the twenty-first century, scientific interest in classic psychedelics has returned and grown as a result of several promising studies, validating earlier research. Here, we review therapeutic research on psilocybin, the classic psychedelic that has been the focus of most recent research. For mood and anxiety disorders, three controlled trials have suggested that psilocybin may decrease symptoms of depression and anxiety in the context of cancer-related psychiatric distress for at least 6 months following a single acute administration. A small, open-label study in patients with treatment-resistant depression showed reductions in depression and anxiety symptoms 3 months after two acute doses. For addiction, small, open-label pilot studies have shown promising success rates for both tobacco and alcohol addiction. Safety data from these various trials, which involve careful screening, preparation, monitoring, and follow-up, indicate the absence of severe drug-related adverse reactions. Modest drug-related adverse effects at the time of medication administration are readily managed. US federal funding has yet to support therapeutic psilocybin research, although such support will be important to thoroughly investigate efficacy, safety, and therapeutic mechanisms.

  14. Yessotoxin, a Promising Therapeutic Tool

    Directory of Open Access Journals (Sweden)

    Amparo Alfonso

    2016-01-01

    Full Text Available Yessotoxin (YTX is a polyether compound produced by dinoflagellates and accumulated in filter feeding shellfish. No records about human intoxications induced by this compound have been published, however it is considered a toxin. Modifications in second messenger levels, protein levels, immune cells, cytoskeleton or activation of different cellular death types have been published as consequence of YTX exposure. This review summarizes the main intracellular pathways modulated by YTX and their pharmacological and therapeutic implications.

  15. Cell kinetics and therapeutic efficiency

    International Nuclear Information System (INIS)

    Andreeff, M.; Abenhardt, W.; Gruner, B.; Stoffner, D.; Mainz Univ.

    1976-01-01

    The study shows that cell kinetics effects correlate with the effects of cytostatic drugs in the tumour model investigated here. It should, however, be noted that even genetically related tumour cell types may react differently to the same cytostatic drug, and that the cell kinetics effects, due to the changes in the cell cycle, cannot be predicted but should be followed with a very fast method, e.g. sequential flan fluorescence cytophotometry, for optimal therapeutic results. (orig./GSE) [de

  16. Conotoxins that confer therapeutic possibilities

    KAUST Repository

    Essack, Magbubah

    2012-06-04

    Cone snails produce a distinctive repertoire of venom peptides that are used both as a defense mechanism and also to facilitate the immobilization and digestion of prey. These peptides target a wide variety of voltage- and ligand-gated ion channels, which make them an invaluable resource for studying the properties of these ion channels in normal and diseased states, as well as being a collection of compounds of potential pharmacological use in their own right. Examples include the United States Food and Drug Administration (FDA) approved pharmaceutical drug, Ziconotide (Prialt; Elan Pharmaceuticals, Inc.) that is the synthetic equivalent of the naturally occurring ?-conotoxin MVIIA, whilst several other conotoxins are currently being used as standard research tools and screened as potential therapeutic drugs in pre-clinical or clinical trials. These developments highlight the importance of driving conotoxin-related research. A PubMed query from 1 January 2007 to 31 August 2011 combined with hand-curation of the retrieved articles allowed for the collation of 98 recently identified conotoxins with therapeutic potential which are selectively discussed in this review. Protein sequence similarity analysis tentatively assigned uncharacterized conotoxins to predicted functional classes. Furthermore, conotoxin therapeutic potential for neurodegenerative disorders (NDD) was also inferred. 2012 by the authors; licensee MDPI.

  17. Diagnostic and therapeutic peroral cholangioscopy

    Directory of Open Access Journals (Sweden)

    Jong Ho Moon

    2012-01-01

    Full Text Available Peroral cholangioscopy (POC provides direct visualization of the bile duct and facilitates diagnostic or therapeutic intervention. The currently available single-operator POC systems are "Mother-baby" scope system, SpyGlass direct visualization system, and direct POC using a regular ultra-slim upper endoscope. Direct POC using an ultra-slim upper endoscope having a larger 2-mm working channel can provide a valuable and economic solution for evaluating bile-duct lesions. Main diagnostic procedures under direct POC are visual characterization and optically guided target biopsy for the indeterminate bile duct lesion. Image-enhanced endoscopy such as narrow-band imaging has shown promise for more detailed evaluation of mucosal abnormality and can be performed under direct POC. Intracorporeal lithotripsy such as electrohydraulic lithotripsy or laser lithotripsy is a main therapeutic intervention of direct POC for patients with bile duct stones that are resistant to conventional endoscopic stone-removal procedures. Besides, tumor ablation therapy, such as photodynamic therapy and argon plasma coagulation may be also performed using direct POC. Further developments of the endoscope and specialized accessories or devices are expected to facilitate diagnostic and therapeutic role of this cholangioscopic procedure.

  18. Avian Diagnostic and Therapeutic Antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, David Sherman [UND SMHS

    2012-12-31

    A number of infectious agents have the potential of causing significant clinical symptomology and even death, but dispite this, the number of incidence remain below the level that supports producing a vaccine. Therapeutic antibodies provide a viable treatment option for many of these diseases. We proposed that antibodies derived from West Nile Virus (WNV) immunized geese would be able to treat WNV infection in mammals and potential humans. We demonstrated that WNV specific goose antibodies are indeed successful in treating WNV infection both prophylactically and therapeutically in a golden hamster model. We demonstrated that the goose derived antibodies are non-reactogenic, i.e. do not cause an inflammatory response with multiple exposures in mammals. We also developed both a specific pathogen free facility to house the geese during the antibody production phase and a patent-pending purification process to purify the antibodies to greater than 99% purity. Therefore, the success of these study will allow a cost effective rapidly producible therapeutic toward clinical testing with the necessary infrastructure and processes developed and in place.

  19. Conotoxins that confer therapeutic possibilities

    KAUST Repository

    Essack, Magbubah; Bajic, Vladimir B.; Archer, John A.C.

    2012-01-01

    Cone snails produce a distinctive repertoire of venom peptides that are used both as a defense mechanism and also to facilitate the immobilization and digestion of prey. These peptides target a wide variety of voltage- and ligand-gated ion channels, which make them an invaluable resource for studying the properties of these ion channels in normal and diseased states, as well as being a collection of compounds of potential pharmacological use in their own right. Examples include the United States Food and Drug Administration (FDA) approved pharmaceutical drug, Ziconotide (Prialt; Elan Pharmaceuticals, Inc.) that is the synthetic equivalent of the naturally occurring ?-conotoxin MVIIA, whilst several other conotoxins are currently being used as standard research tools and screened as potential therapeutic drugs in pre-clinical or clinical trials. These developments highlight the importance of driving conotoxin-related research. A PubMed query from 1 January 2007 to 31 August 2011 combined with hand-curation of the retrieved articles allowed for the collation of 98 recently identified conotoxins with therapeutic potential which are selectively discussed in this review. Protein sequence similarity analysis tentatively assigned uncharacterized conotoxins to predicted functional classes. Furthermore, conotoxin therapeutic potential for neurodegenerative disorders (NDD) was also inferred. 2012 by the authors; licensee MDPI.

  20. Therapeutic drug monitoring of digoxin in cardiac heart failure outpatients: comparisons of two analytical methods

    Directory of Open Access Journals (Sweden)

    Isabel Cristina Medeiros Barros

    2014-01-01

    Full Text Available Objective: To compare two analytical techniques used in the determination of plasma digoxin (LC-MS/MS and immunoassay and to verify which one better answer the need of the clinical monitoring routine of patients with cardiac heart failure. Method: The clinical findings in 15 cardiac heart failure (CHF outpatients of the Cardiac Heart Service of the Goias Federal University Clinical Hospital were investigated. Blood samples of the patients were collected and analysed by Immunoassay and by Liquid Chromatography coupled to Mass Spectrometry (LC-MS/MS. Results: The results of the statistic test (Student p = 0,05 showed a significant difference between the analytical methods: immunoassay concentrations were higher than the concentrations determined by LCMS/ MS. The explanation may be because immunoassay method measures digoxin plus other metabolites and endogenous substances, while the LC-MS/MS method measures only the digoxin molecule. None of the patients, showed relevant clinical data suggestive of digitalis intoxication, even several drugs with potential interaction were associated with treatment. Conclusion: It was concluded, therefore, that LC-MS/MS me thod is safer, more selective and specific than immunoassay, being an option for therapeutic drug monitoring of digoxin, since the reference values would be obtain for digoxinemia by LC-MS/MS.

  1. Statistical significance versus clinical relevance.

    Science.gov (United States)

    van Rijn, Marieke H C; Bech, Anneke; Bouyer, Jean; van den Brand, Jan A J G

    2017-04-01

    In March this year, the American Statistical Association (ASA) posted a statement on the correct use of P-values, in response to a growing concern that the P-value is commonly misused and misinterpreted. We aim to translate these warnings given by the ASA into a language more easily understood by clinicians and researchers without a deep background in statistics. Moreover, we intend to illustrate the limitations of P-values, even when used and interpreted correctly, and bring more attention to the clinical relevance of study findings using two recently reported studies as examples. We argue that P-values are often misinterpreted. A common mistake is saying that P < 0.05 means that the null hypothesis is false, and P ≥0.05 means that the null hypothesis is true. The correct interpretation of a P-value of 0.05 is that if the null hypothesis were indeed true, a similar or more extreme result would occur 5% of the times upon repeating the study in a similar sample. In other words, the P-value informs about the likelihood of the data given the null hypothesis and not the other way around. A possible alternative related to the P-value is the confidence interval (CI). It provides more information on the magnitude of an effect and the imprecision with which that effect was estimated. However, there is no magic bullet to replace P-values and stop erroneous interpretation of scientific results. Scientists and readers alike should make themselves familiar with the correct, nuanced interpretation of statistical tests, P-values and CIs. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  2. Enduring relevance: an introduction to the clinical contributions of K. R. Eissler.

    Science.gov (United States)

    Garcia, Emanuel E

    2009-10-01

    The author offers a personal selection and discussion of papers that epitomize the enduring relevance of K. R. Eissler's contributions to psychoanalytic therapy. The innovations of technique embodied by these works (on parameters, schizophrenia, adolescence, cure, fees, and the treatment of the dying patient) reveal a therapeutic approach that is a natural extension of psychoanalytic science: patient-centered, maximally comprehensive, and appropriately flexible.

  3. Communication techniques for improved acceptance and adherence with therapeutic footwear.

    Science.gov (United States)

    van Netten, Jaap J; Francis, Anthony; Morphet, Ashley; Fortington, Lauren V; Postema, Klaas; Williams, Anita

    2017-04-01

    Clients' acceptance and adherence with orthoses can be influenced by a clinician's communication skills. In this clinical note, we describe two communication techniques, in the context of therapeutic footwear. Person-centred communication involves engaging with and listening to the attitudes of the client towards their condition, as well as discussing acceptance and expectations, in a structured consultation. Building a relationship is crucial and requires clients to feel heard and understood. An important influence on the acceptance and adherence is that a client makes a conscious decision to receive their device. This active receipt can be facilitated through shared decision making, wherein clinicians give clear, relevant and meaningful examples, based on clinical evidence, and ensure this is understood. Two communication techniques for clinicians providing therapeutic footwear are described. These can be adapted for use with provision of other assistive technologies to improve client acceptance and adherence. Clinical relevance Small changes in how clinicians communicate to their clients in daily practice can have a big influence on the subsequent acceptance and adherence with therapeutic footwear and indeed other prescribed assistive technologies.

  4. Does relevance matter in academic policy research?

    DEFF Research Database (Denmark)

    Dredge, Dianne

    2015-01-01

    A reflection on whether relevance matters in tourism policy research. A debate among tourism scholars.......A reflection on whether relevance matters in tourism policy research. A debate among tourism scholars....

  5. Sterol Composition of Clinically Relevant Mucorales and Changes Resulting from Posaconazole Treatment.

    Science.gov (United States)

    Müller, Christoph; Neugebauer, Thomas; Zill, Patrizia; Lass-Flörl, Cornelia; Bracher, Franz; Binder, Ulrike

    2018-05-19

    Mucorales are fungi with increasing importance in the clinics. Infections take a rapidly progressive course resulting in high mortality rates. The ergosterol biosynthesis pathway and sterol composition are of interest, since they are targeted by currently applied antifungal drugs. Nevertheless, Mucorales often exhibit resistance to these drugs, resulting in therapeutic failure. Here, sterol patterns of six clinically relevant Mucorales ( Lichtheimia corymbifera , Lichtheimia ramosa , Mucor circinelloides , Rhizomucor pusillus , Rhizopus arrhizus , and Rhizopus microsporus ) were analysed in a targeted metabolomics fashion after derivatization by gas chromatography-mass spectrometry. Additionally, the effect of posaconazole (POS) treatment on the sterol pattern of R. arrhizus was evaluated. Overall, fifteen different sterols were detected with species dependent variations in the total and relative sterol amount. Sterol analysis from R. arrhizus hyphae confronted with sublethal concentrations of posaconazole revealed the accumulation of 14-methylergosta-8,24-diene-3,6-diol, which is a toxic sterol that was previously only detected in yeasts. Sterol content and composition were further compared to the well-characterized pathogenic mold Aspergillus fumigatus . This work contributes to a better understanding of the ergosterol biosynthesis pathway of Mucorales, which is essential to improve antifungal efficacy, the identification of targets for novel drug design, and to investigate the combinatorial effects of drugs targeting this pathway.

  6. Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use.

    Science.gov (United States)

    Taylor, Charles P; Traynelis, Stephen F; Siffert, Joao; Pope, Laura E; Matsumoto, Rae R

    2016-08-01

    Dextromethorphan (DM) has been used for more than 50years as an over-the-counter antitussive. Studies have revealed a complex pharmacology of DM with mechanisms beyond blockade of N-methyl-d-aspartate (NMDA) receptors and inhibition of glutamate excitotoxicity, likely contributing to its pharmacological activity and clinical potential. DM is rapidly metabolized to dextrorphan, which has hampered the exploration of DM therapy separate from its metabolites. Coadministration of DM with a low dose of quinidine inhibits DM metabolism, yields greater bioavailability and enables more specific testing of the therapeutic properties of DM apart from its metabolites. The development of the drug combination DM hydrobromide and quinidine sulfate (DM/Q), with subsequent approval by the US Food and Drug Administration for pseudobulbar affect, led to renewed interest in understanding DM pharmacology. This review summarizes the interactions of DM with brain receptors and transporters and also considers its metabolic and pharmacokinetic properties. To assess the potential clinical relevance of these interactions, we provide an analysis comparing DM activity from in vitro functional assays with the estimated free drug DM concentrations in the brain following oral DM/Q administration. The findings suggest that DM/Q likely inhibits serotonin and norepinephrine reuptake and also blocks NMDA receptors with rapid kinetics. Use of DM/Q may also antagonize nicotinic acetylcholine receptors, particularly those composed of α3β4 subunits, and cause agonist activity at sigma-1 receptors. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Biology relevant to space radiation

    International Nuclear Information System (INIS)

    Fry, R.J.M.

    1996-01-01

    The biological effects of the radiations to which mankind on earth are exposed are becoming known with an increasing degree of detail. This knowledge is the basis of the estimates of risk that, in turn, fosters a comprehensive and evolving radiation protection system. The substantial body of information has been, and is being, applied to questions about the biological effects of radiation is space and the associated risk estimates. The purpose of this paper is not to recount all the biological effect of radiation but to concentrate on those that may occur as a result from exposure to the radiations encountered in space. In general, the biological effects of radiation in space are the same as those on earth. However, the evidence that the effects on certain tissues by the heaviest-charged particles can be interpreted on the basis of our knowledge about other high-LET radiation is equivocal. This specific question will be discussed in greater detail later. It is important to point out the that there are only limited data about the effects on humans of two components of the radiations in space, namely protons and heavy ions. Thus predictions of effects on space crews are based on experimental systems exposed on earth at rates and fluences that are higher than those in space and one the effects of gamma or x rays with estimates of the equivalent doses using quality factors

  8. Science and the struggle for relevance

    NARCIS (Netherlands)

    Hessels, L.K.|info:eu-repo/dai/nl/304832863

    2010-01-01

    This thesis deals with struggles for relevance of university researchers, their efforts to make their work correspond with ruling standards of relevance and to influence these standards. Its general research question is: How to understand changes in the struggle for relevance of Dutch academic

  9. The Personal Relevance of the Social Studies.

    Science.gov (United States)

    VanSickle, Ronald L.

    1990-01-01

    Conceptualizes a personal-relevance framework derived from Ronald L. VanSickle's five areas of life integrated with four general motivating goals from Abraham Maslow's hierarchy of needs and Richard and Patricia Schmuck's social motivation theory. Illustrates ways to apply the personal relevance framework to make social studies more relevant to…

  10. The Development of Relevance in Information Retrieval

    Directory of Open Access Journals (Sweden)

    Mu-hsuan Huang

    1997-12-01

    Full Text Available This article attempts to investigate the notion of relevance in information retrieval. It discusses various definitions for relevance from historical viewpoints and the characteristics of relevance judgments. Also, it introduces empirical results of important related researches.[Article content in Chinese

  11. A Zebrafish Heart Failure Model for Assessing Therapeutic Agents.

    Science.gov (United States)

    Zhu, Xiao-Yu; Wu, Si-Qi; Guo, Sheng-Ya; Yang, Hua; Xia, Bo; Li, Ping; Li, Chun-Qi

    2018-03-20

    Heart failure is a leading cause of death and the development of effective and safe therapeutic agents for heart failure has been proven challenging. In this study, taking advantage of larval zebrafish, we developed a zebrafish heart failure model for drug screening and efficacy assessment. Zebrafish at 2 dpf (days postfertilization) were treated with verapamil at a concentration of 200 μM for 30 min, which were determined as optimum conditions for model development. Tested drugs were administered into zebrafish either by direct soaking or circulation microinjection. After treatment, zebrafish were randomly selected and subjected to either visual observation and image acquisition or record videos under a Zebralab Blood Flow System. The therapeutic effects of drugs on zebrafish heart failure were quantified by calculating the efficiency of heart dilatation, venous congestion, cardiac output, and blood flow dynamics. All 8 human heart failure therapeutic drugs (LCZ696, digoxin, irbesartan, metoprolol, qiliqiangxin capsule, enalapril, shenmai injection, and hydrochlorothiazide) showed significant preventive and therapeutic effects on zebrafish heart failure (p failure model developed and validated in this study could be used for in vivo heart failure studies and for rapid screening and efficacy assessment of preventive and therapeutic drugs.

  12. Challenges in the development of magnetic particles for therapeutic applications.

    Science.gov (United States)

    Barry, Stephen E

    2008-09-01

    Certain iron-based particle formulations have useful magnetic properties that, when combined with low toxicity and desirable pharmacokinetics, encourage their development for therapeutic applications. This mini-review begins with background information on magnetic particle use as MRI contrast agents and the influence of material size on pharmacokinetics and tissue penetration. Therapeutic investigations, including (1) the loading of bioactive materials, (2) the use of stationary, high-gradient (HG) magnetic fields to concentrate magnetic particles in tissues or to separate material bound to the particles from the body, and (3) the application of high power alternating magnetic fields (AMF) to generate heat in magnetic particles for hyperthermic therapeutic applications are then surveyed. Attention is directed mainly to cancer treatment, as selective distribution to tumors is well-suited to particulate approaches and has been a focus of most development efforts. While magnetic particles have been explored for several decades, their use in therapeutic products remains minimal; a discussion of future directions and potential ways to better leverage magnetic properties and to integrate their use into therapeutic regimens is discussed.

  13. Population pharmacokinetics of phenobarbital in infants with neonatal encephalopathy treated with therapeutic hypothermia.

    Science.gov (United States)

    Shellhaas, Renée A; Ng, Chee M; Dillon, Christina H; Barks, John D E; Bhatt-Mehta, Varsha

    2013-02-01

    Phenobarbital is the first-line treatment for neonatal seizures. Many neonates with hypoxic ischemic encephalopathy are treated with therapeutic hypothermia, and about 40% have clinical seizures. Little is known about the pharmacokinetics of phenobarbital in infants with hypoxic ischemic encephalopathy who undergo therapeutic hypothermia. The objective of this study was to determine the effect of therapeutic hypothermia on phenobarbital pharmacokinetics, taking into account maturational changes. Level 3 neonatal ICU. Infants with hypoxic ischemic encephalopathy and suspected seizures, all treated with phenobarbital. Some of these infants also received treatment with therapeutic hypothermia. None. A retrospective cohort study of 39 infants with hypoxic ischemic encephalopathy treated with phenobarbital (20 were treated with therapeutic hypothermia and 19 were not). Data on phenobarbital plasma concentrations were collected in 39 subjects with hypoxic ischemic encephalopathy with or without therapeutic hypothermia. Using nonlinear mixed-effects modeling, population pharmacokinetics of phenobarbital were developed with a total of 164 plasma concentrations. A one-compartment model best described the pharmacokinetics. The clearance of phenobarbital was linearly related to body weight and matured with increasing age with a maturation half-life of 22.1 days. Therapeutic hypothermia did not influence the pharmacokinetic parameters of phenobarbital. Therapeutic hypothermia does not influence the clearance of phenobarbital after accounting for weight and age. Standard phenobarbital dosing is appropriate for the initial treatment of seizures in neonates with hypoxic ischemic encephalopathy treated with therapeutic hypothermia.

  14. Therapeutic Basis of Clinical Pain Modulation

    Science.gov (United States)

    Kirkpatrick, Daniel R.; McEntire, Dan M.; Hambsch, Zakary J.; Kerfeld, Mitchell J.; Smith, Tyler A.; Reisbig, Mark D.; Youngblood, Charles F.

    2015-01-01

    Abstract Pain is a hallmark of almost all bodily ailments and can be modulated by agents, including analgesics and anesthetics that suppress pain signals in the central nervous system. Defects in the modulatory systems, including the endogenous pain‐inhibitory pathways, are a major factor in the initiation and chronicity of pain. Thus, pain modulation is particularly applicable to the practice of medicine. This review summarizes the existing literature on pain modulation. Here, we critically reviewed the literature from PubMed on pain modulation published primarily within the past 5 years in high impact journals. Specifically, we have discussed important anatomical landmarks of pain modulation and outlined the endogenous networks and underlying mechanisms of clinically relevant pain modulatory methods. The Gate Control Theory is briefly presented with discussion on the capacity of pain modulation to cause both hyper‐ and hypoalgesia. An emphasis has been given to highlight key areas in pain research that, because of unanswered questions or therapeutic potential, merit additional scientific scrutiny. The information presented in this paper would be helpful in developing novel therapies, metrics, and interventions for improved patient management. PMID:25962969

  15. New Therapeutic Targets in Soft Tissue Sarcoma

    Science.gov (United States)

    Demicco, Elizabeth G; Maki, Robert G; Lev, Dina C.; Lazar, Alexander J

    2012-01-01

    Soft tissue sarcomas are an uncommon and diverse group of more than 50 mesenchymal malignancies. The pathogenesis of many of these is poorly understood, but others have begun to reveal the secrets of their inner workings. With considerable effort over recent years, soft tissue sarcomas have increasingly been classified on the basis of underlying molecular alterations. In turn, this has allowed the development and application of targeted agents in several specific, molecularly defined, sarcoma subtypes. This review will focus the rationale for targeted therapy in sarcoma, with emphasis on the relevance of specific molecular factors and pathways in both translocation-associated sarcomas and in genetically complex tumors. In addition, we will address some of the early successes in sarcoma targeted therapy as well as a few challenges and disappointments in this field. Finally we will discuss several possible opportunities represented by poorly understood, but potentially promising new therapeutic targets, as well as several novel biologic agents currently in preclinical and early phase I/II trials. This will provide the reader with context for understanding the current state this field and a sense of where it may be headed in the coming years. PMID:22498582

  16. TRAIL death receptors and cancer therapeutics

    International Nuclear Information System (INIS)

    Huang Ying; Sheikh, M. Saeed

    2007-01-01

    Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) also known as Apo2L is an apoptotic molecule that belongs to the tumor necrosis factor superfamily of cytokines. It mediates its apoptotic effects via its cognate death receptors including DR4 and DR5. Agonistic monoclonal antibodies have also been developed that selectively activate TRAIL death receptors to mediate apoptosis. Multiple clinically relevant agents also upregulate the expression of TRAIL death receptors, and cooperate with TRAIL as well as DR4 and DR5-specific agonistic antibodies to exhibit tumor cell killing. TRAIL is currently in phase I clinical trials, whereas DR4 and DR5-specific agonistic antibodies have been tested in phase I and II studies. Thus, TRAIL has clearly distinguished itself from the other family members including TNF-alpha and FasL both of which could not make it to the clinic due to their toxic nature. It is therefore, evident that the future of TRAIL-based therapeutic approaches looks brighter

  17. Pharmacokinetics and toxicology of therapeutic proteins: Advances and challenges

    Science.gov (United States)

    Vugmeyster, Yulia; Xu, Xin; Theil, Frank-Peter; Khawli, Leslie A; Leach, Michael W

    2012-01-01

    Significant progress has been made in understanding pharmacokinetics (PK), pharmacodynamics (PD), as well as toxicity profiles of therapeutic proteins in animals and humans, which have been in commercial development for more than three decades. However, in the PK arena, many fundamental questions remain to be resolved. Investigative and bioanalytical tools need to be established to improve the translation of PK data from animals to humans, and from in vitro assays to in vivo readouts, which would ultimately lead to a higher success rate in drug development. In toxicology, it is known, in general, what studies are needed to safely develop therapeutic proteins, and what studies do not provide relevant information. One of the major complicating factors in nonclinical and clinical programs for therapeutic proteins is the impact of immunogenicity. In this review, we will highlight the emerging science and technology, as well as the challenges around the pharmacokinetic- and safety-related issues in drug development of mAbs and other therapeutic proteins. PMID:22558487

  18. Psychological treatment and therapeutic change in incarcerated rapists

    Directory of Open Access Journals (Sweden)

    Ana Martínez-Catena

    2017-01-01

    Full Text Available Abstract Most Spanish prisons provide specialised treatment for incarcerated sex offenders, both rapists and child molesters. This treatment is a cognitive-behavioural intervention that has shown relative effectiveness in previous research. With regard to offenders’ rehabilitation, recidivism assessments are necessary as a final measure of treatment effectiveness. However, the evaluation of recidivism by itself does not provide sufficient information on the treatment process and the specific effects that treated subjects could undergo. This paper aims to analyse the therapeutic effectiveness of psychological treatment provided to rapists (in general, males sentenced for committing a sexual offence against women. To this aim, a group of treated rapists (N=153 serving a sentence in prison was analysed. Using a specially designed scale (PASSO, the global therapeutic change and ten specific variables (including assertiveness, readiness to change, cognitive distortions, impulsivity, etc. were assessed. The within-subjects comparison showed that treated sex offenders improved, in therapeutic terms, globally as well as in most of the specific variables assessed (improvements not experimented by the control group. Also, different therapeutic subscales showed relevant associations between them. The findings regarding treatment effectiveness are discussed.

  19. Defining the therapeutic time window for suppressing the inflammatory prostaglandin E2 signaling after status epilepticus

    Science.gov (United States)

    Du, Yifeng; Kemper, Timothy; Qiu, Jiange; Jiang, Jianxiong

    2016-01-01

    Neuroinflammation is a common feature in nearly all neurological and some psychiatric disorders. Resembling its extraneural counterpart, neuroinflammation can be both beneficial and detrimental depending on the responding molecules. The overall effect of inflammation on disease progression is highly dependent on the extent of inflammatory mediator production and the duration of inflammatory induction. The time-dependent aspect of inflammatory responses suggests that the therapeutic time window for quelling neuroinflammation might vary with molecular targets and injury types. Therefore, it is important to define the therapeutic time window for anti-inflammatory therapeutics, as contradicting or negative results might arise when different treatment regimens are utilized even in similar animal models. Herein, we discuss a few critical factors that can help define the therapeutic time window and optimize treatment paradigm for suppressing the cyclooxygenase-2/prostaglandin-mediated inflammation after status epilepticus. These determinants should also be relevant to other anti-inflammatory therapeutic strategies for the CNS diseases. PMID:26689339

  20. MicroRNAs in cancer therapeutics: "from the bench to the bedside".

    Science.gov (United States)

    Monroig-Bosque, Paloma del C; Rivera, Carlos A; Calin, George A

    2015-01-01

    MicroRNAs (miRNAs) are non-coding RNA transcripts that regulate physiological processes by targeting proteins directly. Their involvement in research has been robust, and evidence of their regulative functions has granted them the title: master regulators of the human genome. In cancer, they are considered important therapeutic agents, due to the fact that their aberrant expression contributes to disease development, progression, metastasis, therapeutic response and patient overall survival. This has endeavored fields of biomedical sciences to invest in developing and exploiting miRNA-based therapeutics thoroughly. Herein we highlight relevant ongoing/open clinical trials involving miRNAs and cancer.

  1. Therapeutic irradiation and brain injury

    International Nuclear Information System (INIS)

    Sheline, G.E.; Wara, W.M.; Smith, V.

    1980-01-01

    This is a review and reanalysis of the literature on adverse effects of therapeutic irradiation on the brain. Reactions have been grouped and considered according to time of appearance. The emphasis of the analysis is on delayed reactions, especially those that occur from a few months to several years after irradiation. All dose specifications were converted into equivalent megavoltage rads. The data were analyzed in terms of total dose, overall treatment time and number of treatment fractions. Also discussed were acute radiation reactions, early delayed radiation reactions, somnolence and leukoencephalopathy post-irradiation/chemotherapy and combined effects of radiation and chemotherapy

  2. Nostalgia's place among self-relevant emotions.

    Science.gov (United States)

    van Tilburg, Wijnand A P; Wildschut, Tim; Sedikides, Constantine

    2017-07-24

    How is nostalgia positioned among self-relevant emotions? We tested, in six studies, which self-relevant emotions are perceived as most similar versus least similar to nostalgia, and what underlies these similarities/differences. We used multidimensional scaling to chart the perceived similarities/differences among self-relevant emotions, resulting in two-dimensional models. The results were revealing. Nostalgia is positioned among self-relevant emotions characterised by positive valence, an approach orientation, and low arousal. Nostalgia most resembles pride and self-compassion, and least resembles embarrassment and shame. Our research pioneered the integration of nostalgia among self-relevant emotions.

  3. Binge-eating disorder: Clinical and therapeutic advances.

    Science.gov (United States)

    Hutson, Peter H; Balodis, Iris M; Potenza, Marc N

    2018-02-01

    Binge-eating disorder (BED) is the most prevalent eating disorder with estimates of 2-5% of the general adult population. Nonetheless, its pathophysiology is poorly understood. Furthermore, there exist few therapeutic options for its effective treatment. Here we review the current state of binge-eating neurobiology and pharmacology, drawing from clinical therapeutic, neuroimaging, cognitive, human genetic and animal model studies. These studies, which are still in their infancy, indicate that while there are many gaps in our knowledge, several key neural substrates appear to underpin binge-eating and may be conserved between human and animals. This observation suggests that behavioral intermediate phenotypes or endophenotypes relevant to BED may be modeled in animals, facilitating the identification and testing of novel pharmacological targets. The development of novel, safe and effective pharmacological therapies for the treatment of BED will enhance the ability of clinicians to provide optimal care for people with BED. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Podocytes from the diagnostic and therapeutic point of view.

    Science.gov (United States)

    Müller-Deile, Janina; Schiffer, Mario

    2017-08-01

    The central role of podocytes in glomerular diseases makes this cell type an interesting diagnostic tool as well as a therapeutic target. In this review, we discuss the current literature on the use of podocytes and podocyte-specific markers as non-invasive diagnostic tools in different glomerulopathies. Furthermore, we highlight the direct effects of drugs currently used to treat primary glomerular diseases and describe their direct cellular effects on podocytes. A new therapeutic potential is seen in drugs targeting the podocytic actin cytoskeleton which is essential for podocyte foot process structure and function. Incubation of cultured human podocyte cell lines with sera from patients with active glomerular diseases is currently also used to identify novel circulating factors with pathophysiological relevance for the glomerular filtration barrier. In addition, treatment of detached urinary podocytes from patients with substances that restore their cytoskeleton might serve as a novel personalized tool to estimate their potential for podocyte recovery ex vivo.

  5. The pragmatics of therapeutic interaction: an empirical study.

    Science.gov (United States)

    Lepper, Georgia

    2009-10-01

    The research reported in this article aims to demonstrate a method for the systematic study of the therapist/patient interaction in psychoanalytic psychotherapy, drawing upon the tradition and methods of 'pragmatics'--the study of language in interaction. A brief introduction to the discipline of pragmatics demonstrates its relevance to the contemporary focus of clinical theory on the here-and-now dynamics of the relationship between analyst and patient. This is followed by a detailed study of five segments from the transcript of a therapeutic dialogue, drawn from a brief psychoanalytic psychotherapy, in which therapist and patient negotiate the meaning of the patient's symptom: Is it psychosomatic? The research seeks to show how the therapeutic process can be observed and studied as an interactional achievement, grounded in general and well-studied procedures through which meaning is intersubjectively developed and shared. Implications of the analysis for clinical theory and practice, and further research, are discussed.

  6. Frizzled Receptors as Potential Therapeutic Targets in Human Cancers

    Directory of Open Access Journals (Sweden)

    Chui-Mian Zeng

    2018-05-01

    Full Text Available Frizzled receptors (FZDs are a family of seven-span transmembrane receptors with hallmarks of G protein-coupled receptors (GPCRs that serve as receptors for secreted Wingless-type (WNT ligands in the WNT signaling pathway. Functionally, FZDs play crucial roles in regulating cell polarity, embryonic development, cell proliferation, formation of neural synapses, and many other processes in developing and adult organisms. In this review, we will introduce the basic structural features and review the biological function and mechanism of FZDs in the progression of human cancers, followed by an analysis of clinical relevance and therapeutic potential of FZDs. We will focus on the development of antibody-based and small molecule inhibitor-based therapeutic strategies by targeting FZDs for human cancers.

  7. EXETRA Perspectives: Concepts in Therapeutic Recreation.

    Science.gov (United States)

    Neal, Larry L.; Edginton, Christopher R.

    Fifteen papers address issues in therapeutic recreation for disabled persons from the perspectives of practitioners, educators, and students. The following papers are presented. "Therapeutic Recreation Service: The Past and Challenging Present" (H. Sessoms); "Therapeutic Recreatiion in an Era of Limits: A Crisis...A Challenge... An Opportunity"…

  8. Toxicological relevance of emerging contaminants for drinking water quality

    OpenAIRE

    Schriks, M.; Heringa, M.B.; van der Kooij, M.M.E.; de Voogt, P.; van Wezel, A.P.

    2010-01-01

    The detection of many new compounds in surface water, groundwater and drinking water raises considerable public concern, especially when human health based guideline values are not available it is questioned if detected concentrations affect human health. In an attempt to address this question, we derived provisional drinking water guideline values for a selection of 50 emerging contaminants relevant for drinking water and the water cycle. For only 10 contaminants, statutory guideline values ...

  9. practical management of therapeutic diphenylhydantoin ...

    African Journals Online (AJOL)

    serum was then analysed in triplicate for DPH content using an ... concentrations of each individual, generated on the .... desire of the clinician not to overdose the patient. ... intuitively easy to understand and, once learnt, extremely user-.

  10. Diagnostic and therapeutic radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Russell, W J [Radiation Effects Research Foundation, Hiroshima (Japan)

    1975-09-01

    Diagnostic and therapeutic radiology were studied as possible contaminants in the evaluations of A-bomb survivors in the ABCC-JNIH Adult Health Study for radiation effects. Hiroshima and Nagasaki subjects received X-ray examinations elsewhere within three months of their ABCC visits at rates of 23 and 12%, respectively. Medical X-ray examinations were more frequent among survivors than comparison subjects. Hiroshima and Nagasaki radiologic practice steadily increased since 1948, and differed markedly by city. From 1946-70 the Hiroshima and Nagasaki X-ray bone marrow doses were 2,300 and 1,000 g-rads, respectively. By 1970, cumulated medical X-ray doses approximated A-bomb doses at distances from the hypocenters of 2,000 m in Hiroshima and 2,800 m in Nagasaki. ABCC X-ray examination doses per subject are routinely updated for comparison with A-bomb doses. Each subject's reported fluoroscopy, photofluorography and radiation therapy exposure elsewhere are for future reference. Dental radiography, though increasing, was not currently an important contributor to survivors' overall exposure. Radiation therapy exposures of 137 subjects were confirmed, and doses estimated for most. Two-thirds the treatments were for malignancies; therapy differed markedly by city; and five cancers possibly arose from earlier radiation therapy. This underscores the importance of considering diagnostic and therapeutic radiology when attributing diseases to the atomic bombs.

  11. [Therapeutic Aggressiveness and Liquid Oncology].

    Science.gov (United States)

    Barón Duarte, F J; Rodríguez Calvo, M S; Amor Pan, J R

    2017-01-01

    Aggressiveness criteria proposed in the scientific literature a decade ago provide a quality judgment and are a reference in the care of patients with advanced cancer, but their use is not generalized in the evaluation of Oncology Services. In this paper we analyze the therapeutic aggressiveness, according to standard criteria, in 1.001 patients with advanced cancer who died in our Institution between 2010 and 2013. The results seem to show that aggressiveness at the end of life is present more frequently than experts recommend. About 25% of patients fulfill at least one criterion of aggressiveness. This result could be explained by a liquid Oncology which does not prioritize the patient as a moral subject in the clinical appointment. Medical care is oriented to necessities and must be articulated in a model focused on dignity and communication. Its implementation through Advanced Care Planning, consideration of patient's values and preferences, and Limitation of therapeutic effort are ways to reduce aggressiveness and improve clinical practice at the end of life. We need to encourage synergic and proactive attitudes, adding the best of cancer research with the best clinical care for the benefit of human being, moral subject and main goal of Medicine.

  12. Molecules of various pharmacologically-relevant sizes can cross the ultrasound-induced blood-brain barrier opening in vivo.

    Science.gov (United States)

    Choi, James J; Wang, Shougang; Tung, Yao-Sheng; Morrison, Barclay; Konofagou, Elisa E

    2010-01-01

    Focused ultrasound (FUS) is hereby shown to noninvasively and selectively deliver compounds at pharmacologically relevant molecular weights through the opened blood-brain barrier (BBB). A complete examination on the size of the FUS-induced BBB opening, the spatial distribution of the delivered agents and its dependence on the agent's molecular weight were imaged and quantified using fluorescence microscopy. BBB opening in mice (n=13) was achieved in vivo after systemic administration of microbubbles and subsequent application of pulsed FUS (frequency: 1.525MHz, peak-rarefactional pressure in situ: 570 kPa) to the left murine hippocampus through the intact skin and skull. BBB-impermeant, fluorescent-tagged dextrans at three distinct molecular weights spanning over several orders of magnitude were systemically administered and acted as model therapeutic compounds. First, dextrans of 3 and 70 kDa were delivered trans-BBB while 2000 kDa dextran was not. Second, compared with 70 kDa dextran, a higher concentration of 3 kDa dextran was delivered through the opened BBB. Third, the 3 and 70 kDa dextrans were both diffusely distributed throughout the targeted brain region. However, high concentrations of 70 kDa dextran appeared more punctated throughout the targeted region. In conclusion, FUS combined with microbubbles opened the BBB sufficiently to allow passage of compounds of at least 70 kDa, but not greater than 2000 kDa into the brain parenchyma. This noninvasive and localized BBB opening technique could, thus, provide a unique means for the delivery of compounds of several magnitudes of kDa that include agents with shown therapeutic promise in vitro but whose in vivo translation has been hampered by their associated BBB impermeability. (E-mail: ek2191@columbia.edu).

  13. Structurally Based Therapeutic Evaluation: A Therapeutic and Practical Approach to Teaching Medicinal Chemistry.

    Science.gov (United States)

    Alsharif, Naser Z.; And Others

    1997-01-01

    Explains structurally based therapeutic evaluation of drugs, which uses seven therapeutic criteria in translating chemical and structural knowledge into therapeutic decision making in pharmaceutical care. In a Creighton University (Nebraska) medicinal chemistry course, students apply the approach to solve patient-related therapeutic problems in…

  14. The therapeutic relationship after psychiatric admission.

    LENUS (Irish Health Repository)

    Roche, Eric

    2014-03-01

    The therapeutic relationship is one of the most central and important factors in the treatment of mental health disorders. A better therapeutic relationship is associated with service engagement, medication adherence, and satisfaction with services. This study aimed to compare the demographic and clinical factors associated with the therapeutic relationship in voluntarily and involuntarily admitted psychiatric service users. We found that individuals who had been admitted involuntarily, who had a diagnosis of a psychotic disorder, and who reported higher levels of perceived pressures on admission were more likely to have a poorer therapeutic relationship with their consultant psychiatrist. Greater levels of insight and treatment satisfaction, together with higher levels of procedural justice experienced on admission, were associated with a better therapeutic relationship. We found that the level of perceived coercion on admission was not related to the therapeutic relationship. Targeted interventions to improve the therapeutic relationship, particularly for involuntarily admitted service users, are discussed.

  15. Serum anti-Müllerian hormone concentrations before and after treatment of an ovarian granulosa cell tumour in a cat

    Directory of Open Access Journals (Sweden)

    Laura A Heaps

    2017-08-01

    Full Text Available Case summary A 15-year-old female cat was presented for investigation of progressive behavioural changes, polyuria, polydipsia and periuria. An ovarian granulosa cell tumour was identified and the cat underwent therapeutic ovariohysterectomy (OHE. The cat’s clinical signs resolved, but 6 months later it was diagnosed as having an anaplastic astrocytoma and was euthanased. Serum anti-Müllerian hormone (AMH concentration prior to OHE was increased vs a control group of entire and neutered female cats. Following OHE, serum AMH concentration decreased to <1% of the original value. Relevance and novel information Serum AMH measurement may represent a novel diagnostic and monitoring tool for functional ovarian neoplasms in cats.

  16. Current issues of RNAi therapeutics delivery and development.

    Science.gov (United States)

    Haussecker, D

    2014-12-10

    12 years following the discovery of the RNAi mechanism in Man, a number of RNAi therapeutics development candidates have emerged with profiles suggesting that they could become drugs of significant medical importance for diseases like TTR amyloidosis, HBV, solid cancers, and hemophilia. Despite this robust progress, the perception of RNAi therapeutics has been on a roller-coaster ride driven not only by science, but also regulatory trends, the stock markets, and Big Pharma business development decisions [1]. This presentation provides an update on the current state of RNAi therapeutics development with a particular focus on what RNAi delivery can achieve today and key challenges to be overcome to expand therapeutic opportunities. The delivery of RNAi triggers to disease-relevant cell types clearly represents the rate-limiting factor in broadly expanding the applicability of RNAi therapeutics. Today, with at least 3 delivery options (lipid nanoparticles/LNPs, GalNAc-siRNA conjugates, Dynamic PolyConjugates/DPCs) for which profound gene knockdowns have been demonstrated in non-human primates and in the clinic, RNAi therapeutics should in principle be able to address most diseases related to gene expression in the liver. Given the central importance of the liver in systemic physiology, this already represents a significant therapeutic and commercial opportunity rivaling that of e.g. monoclonal antibodies. Beyond the liver, there is a reason to believe that current RNAi therapeutics technologies can address a number of solid tumors (e.g. LNPs), diseases of the eye (e.g. self-delivering RNAi triggers) as well as diseases involving the respiratory epithelium (e.g. aerosolized LNPs), certain phagocytic cells (LNPs), hematopoietic stem cells and their progeny (lentiviral DNA-directed RNAi), vascular endothelial cells (cationic lipoplexes), and certain cell types in the kidney (self-delivering RNAi triggers, DPCs; Table 1). Despite this success, there has been a sense that

  17. Discovery and design of carbohydrate-based therapeutics.

    Science.gov (United States)

    Cipolla, Laura; Araújo, Ana C; Bini, Davide; Gabrielli, Luca; Russo, Laura; Shaikh, Nasrin

    2010-08-01

    Till now, the importance of carbohydrates has been underscored, if compared with the two other major classes of biopolymers such as oligonucleotides and proteins. Recent advances in glycobiology and glycochemistry have imparted a strong interest in the study of this enormous family of biomolecules. Carbohydrates have been shown to be implicated in recognition processes, such as cell-cell adhesion, cell-extracellular matrix adhesion and cell-intruder recognition phenomena. In addition, carbohydrates are recognized as differentiation markers and as antigenic determinants. Due to their relevant biological role, carbohydrates are promising candidates for drug design and disease treatment. However, the growing number of human disorders known as congenital disorders of glycosylation that are being identified as resulting from abnormalities in glycan structures and protein glycosylation strongly indicates that a fast development of glycobiology, glycochemistry and glycomedicine is highly desirable. The topics give an overview of different approaches that have been used to date for the design of carbohydrate-based therapeutics; this includes the use of native synthetic carbohydrates, the use of carbohydrate mimics designed on the basis of their native counterpart, the use of carbohydrates as scaffolds and finally the design of glyco-fused therapeutics, one of the most recent approaches. The review covers mainly literature that has appeared since 2000, except for a few papers cited for historical reasons. The reader will gain an overview of the current strategies applied to the design of carbohydrate-based therapeutics; in particular, the advantages/disadvantages of different approaches are highlighted. The topic is presented in a general, basic manner and will hopefully be a useful resource for all readers who are not familiar with it. In addition, in order to stress the potentialities of carbohydrates, several examples of carbohydrate-based marketed therapeutics are given

  18. Novel therapeutic approaches in chondrosarcoma.

    Science.gov (United States)

    Polychronidou, Genovefa; Karavasilis, Vasilios; Pollack, Seth M; Huang, Paul H; Lee, Alex; Jones, Robin L

    2017-03-01

    Chondrosarcoma is a malignant tumor of bones, characterized by the production of cartilage matrix. Due to lack of effective treatment for advanced disease, the clinical management of chondrosarcomas is exceptionally challenging. Current research focuses on elucidating the molecular events underlying the pathogenesis of this rare bone malignancy, with the goal of developing new molecularly targeted therapies. Signaling pathways suggested to have a role in chondrosarcoma include Hedgehog, Src, PI3k-Akt-mTOR and angiogenesis. Mutations in IDH1/2, present in more than 50% of primary conventional chondrosarcomas, make the development of IDH inhibitors a promising treatment option. The present review discusses the preclinical and early clinical data on novel targeted therapeutic approaches in chondrosarcoma.

  19. Toxin-Based Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    Itai Benhar

    2010-10-01

    Full Text Available Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin.

  20. Toxin-Based Therapeutic Approaches

    Science.gov (United States)

    Shapira, Assaf; Benhar, Itai

    2010-01-01

    Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin. PMID:22069564

  1. Angiogenesis and Its Therapeutic Opportunities

    Directory of Open Access Journals (Sweden)

    So Young Yoo

    2013-01-01

    Full Text Available Angiogenesis plays critical roles in human physiology that range from reproduction and fetal growth to wound healing and tissue repair. The sophisticated multistep process is tightly regulated in a spatial and temporal manner by “on-off switch signals” between angiogenic factors, extracellular matrix components, and endothelial cells. Uncontrolled angiogenesis may lead to several angiogenic disorders, including vascular insufficiency (myocardial or critical limb ischemia and vascular overgrowth (hemangiomas, vascularized tumors, and retinopathies. Thus, numerous therapeutic opportunities can be envisaged through the successful understanding and subsequent manipulation of angiogenesis. Here, we review the clinical implications of angiogenesis and discuss pro- and antiangiogenic agents that offer potential therapy for cancer and other angiogenic diseases.

  2. Therapeutic target for protozoal diseases

    Science.gov (United States)

    Rathore, Dharmendar [Blacksburg, VA; Jani, Dewal [Blacksburg, VA; Nagarkatti, Rana [Blacksburg, VA

    2008-10-21

    A novel Fasciclin Related Adhesive Protein (FRAP) from Plasmodium and related parasites is provided as a target for therapeutic intervention in diseases caused by the parasites. FRAP has been shown to play a critical role in adhesion to, or invasion into, host cells by the parasite. Furthermore, FRAP catalyzes the neutralization of heme by the parasite, by promoting its polymerization into hemozoin. This invention provides methods and compositions for therapies based on the administration of protein, DNA or cell-based vaccines and/or antibodies based on FRAP, or antigenic epitopes of FRAP, either alone or in combination with other parasite antigens. Methods for the development of compounds that inhibit the catalytic activity of FRAP, and diagnostic and laboratory methods utilizing FRAP are also provided.

  3. Therapeutic Plasmapheresis in Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    Zeynep Kendi Celebi

    2013-02-01

    Full Text Available In 1960's, with succesfully renal transplantations, acute rejection became to be a serious problem for graft survival. From 1965 to 2010, with the introduction of new immunosuppressant agents such as cyclosporine, mycophenolate mofetile and tacrolimus, the acute rejection rates declined from 80% to 10% . There is an ongoing gradual improvement in allograft survival. Use of Therapeutic plasma exchange (TPE is not evidence based treatment, but TPE is necessary for pre- and also post transplantation in patients with DSA. TPE is also a main treatment for antibody mediated rejection (AMR , but in clinical practice the duration and frequency of TPE and individual difference of antibody production is unclear. There is a requirement for more specific antibody elimination. Further randomised controlled studies are needed to elucidate TPE use before and after kidney transplantation. [Dis Mol Med 2013; 1(1.000: 8-10

  4. Therapeutical uses of 131I

    International Nuclear Information System (INIS)

    Lago, Graciela.

    1994-01-01

    Physiology of thyroid gland, pathology of thyroid , papillary, follicular cancer is considered together as differentiated thyroid cancer with very good results under therapy with iodine, invitro determination of calcitonin, search of metastasis, anaplastic carcinoma, as indifferentiated carcinoma with similar results as medullary carcinoma. This work gives a protocol for therapeutical use of 131I , in hyperthyroidism due to Graves-Basedow disease, thyrotoxic adenoma or Plummer disease, toxic multi nodular goiter, subacute thyroiditis. Is studied too the treatment with pharmaceuticals, surgery and radioactive iodine. A recommended use of each and protocol for iodine administration, fixed dose technique, dose estimation,absorbed dose, recommendations about when to use and not use 131I are included in this work

  5. Therapeutic interventions in cerebral palsy.

    Science.gov (United States)

    Patel, Dilip R

    2005-11-01

    Various therapeutic interventions have been used in the management of children with cerebral palsy. Traditional physiotherapy and occupational therapy are widely used interventions and have been shown to be of benefit in the treatment of cerebral palsy. Evidence in support of the effectiveness of the neurodevelopmental treatment is equivocal at best. There is evidence to support the use and effectiveness of neuromuscular electrical stimulation in children with cerebral palsy. The effectiveness of many other interventions used in the treatment of cerebral palsy has not been clearly established based on well-controlled trials. These include: sensory integration, body-weight support treadmill training, conductive education, constraint-induced therapy, hyperbaric oxygen therapy, and the Vojta method. This article provides an overview of salient aspects of popular interventions used in the management of children with cerebral palsy.

  6. Guidelines for Rational Cancer Therapeutics

    Directory of Open Access Journals (Sweden)

    Byunghee Yoo

    2017-12-01

    Full Text Available Traditionally, cancer therapy has relied on surgery, radiation therapy, and chemotherapy. In recent years, these interventions have become increasingly replaced or complemented by more targeted approaches that are informed by a deeper understanding of the underlying biology. Still, the implementation of fully rational patient-specific drug design appears to be years away. Here, we present a vision of rational drug design for cancer that is defined by two major components: modularity and image guidance. We suggest that modularity can be achieved by combining a nanocarrier and an oligonucleotide component into the therapeutic. Image guidance can be incorporated into the nanocarrier component by labeling with a specific imaging reporter, such as a radionuclide or contrast agent for magnetic resonance imaging. While limited by the need for additional technological advancement in the areas of cancer biology, nanotechnology, and imaging, this vision for the future of cancer therapy can be used as a guide to future research endeavors.

  7. Therapeutic options for lip augmentation.

    Science.gov (United States)

    Segall, Lorne; Ellis, David A F

    2007-11-01

    Aesthetic ideals vary with emerging fashion trends and within different cultures. However, over the past few decades, fuller lips have been considered a desirable trait. Many younger patients are presenting for lip augmentation to achieve the sought-after look commonly seen in many fashion magazines. In addition, as individuals age, they lose lip volume, with a thinning of the red lip, some effacement of the vermillion border, and elongation and flattening of the white portion of the lip. Rejuvenation of the lips plays a key role in restoring a more youthful appearance. As a result, lip augmentation appeals to a wide spectrum of patients who present with various different aesthetic goals and expectations. Numerous therapeutic options exist for aesthetic lip augmentation, ranging from temporary and permanent injectable fillers to implants and other surgical techniques.

  8. Relevance: An Interdisciplinary and Information Science Perspective

    Directory of Open Access Journals (Sweden)

    Howard Greisdorf

    2000-01-01

    Full Text Available Although relevance has represented a key concept in the field of information science for evaluating information retrieval effectiveness, the broader context established by interdisciplinary frameworks could provide greater depth and breadth to on-going research in the field. This work provides an overview of the nature of relevance in the field of information science with a cursory view of how cross-disciplinary approaches to relevance could represent avenues for further investigation into the evaluative characteristics of relevance as a means for enhanced understanding of human information behavior.

  9. Therapeutic patient education in heart failure: do studies provide sufficient information about the educational programme?

    Science.gov (United States)

    Albano, Maria Grazia; Jourdain, Patrick; De Andrade, Vincent; Domenke, Aukse; Desnos, Michel; d'Ivernois, Jean-François

    2014-05-01

    Therapeutic patient education programmes on heart failure have been widely proposed for many years for heart failure patients, but their efficiency remains questionable, partly because most articles lack a precise programme description, which makes comparative analysis of the studies difficult. To analyse the degree of precision in describing therapeutic patient education programmes in recent randomized controlled trials. Three major recent recommendations on therapeutic patient education in heart failure inspired us to compile a list of 23 relevant items that an 'ideal' description of a therapeutic patient education programme should contain. To discover the extent to which recent studies into therapeutic patient education in heart failure included these items, we analysed 19 randomized controlled trials among 448 articles published in this field from 2005 to 2012. The major elements required to describe a therapeutic patient education programme were present, but some other very important pieces of information were missing in most of the studies we analysed: the patient's educational needs, health literacy, projects, expectations regarding therapeutic patient education and psychosocial status; the educational methodology used; outcomes evaluation; and follow-up strategies. Research into how therapeutic patient education can help heart failure patients will be improved if more precise descriptions of patients, educational methodology and evaluation protocols are given by authors, ideally in a standardized format. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  10. An analytical model for nanoparticles concentration resulting from infusion into poroelastic brain tissue.

    Science.gov (United States)

    Pizzichelli, G; Di Michele, F; Sinibaldi, E

    2016-02-01

    We consider the infusion of a diluted suspension of nanoparticles (NPs) into poroelastic brain tissue, in view of relevant biomedical applications such as intratumoral thermotherapy. Indeed, the high impact of the related pathologies motivates the development of advanced therapeutic approaches, whose design also benefits from theoretical models. This study provides an analytical expression for the time-dependent NPs concentration during the infusion into poroelastic brain tissue, which also accounts for particle binding onto cells (by recalling relevant results from the colloid filtration theory). Our model is computationally inexpensive and, compared to fully numerical approaches, permits to explicitly elucidate the role of the involved physical aspects (tissue poroelasticity, infusion parameters, NPs physico-chemical properties, NP-tissue interactions underlying binding). We also present illustrative results based on parameters taken from the literature, by considering clinically relevant ranges for the infusion parameters. Moreover, we thoroughly assess the model working assumptions besides discussing its limitations. While not laying any claims of generality, our model can be used to support the development of more ambitious numerical approaches, towards the preliminary design of novel therapies based on NPs infusion into brain tissue. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Search for relevant indications for selenium supplementation in thyroid diseases.

    Science.gov (United States)

    Wojciechowska-Durczynska, Katarzyna; Lewinski, Andrzej

    2017-08-01

    Selenium plays a significant role in the thyroid function and its deficiency is considered by some authors to be a cause of thyroid disorders. The potential therapeutic influence of selenium supplementation in thyroid disease was investigated in several studies and some results were encouraging, however results were inconsistent and did not allow conclusion to be drawn. For that reason, we have performed a review study on relevance of selenium supplementation in thyroid disease. Till now, there is no strong evidence that selenium supplementation leads to clinical improvement in the course of autoimmune thyroiditis, nodular goitre or thyroid cancer. On the other hand, there is some evidence that selenium is effective in the treatment of orbitopathy; thus, the European Group on Graves' Orbitopathy (EUGOGO) recommends selenium administration in mild active orbitopathy.

  12. Tumor PDT-associated immune response: relevance of sphingolipids

    Science.gov (United States)

    Korbelik, Mladen; Merchant, Soroush; Separovic, Duska M.

    2010-02-01

    Sphingolipids have become recognized as essential effector molecules in signal transduction with involvement in various aspects of cell function and death, immune response and cancer treatment response. Major representatives of sphingolipids family, ceramide, sphingosine and sphingosine-1-phosphate (S1P), have attracted interest in their relevance to tumor response to photodynamic therapy (PDT) because of their roles as enhancers of apoptosis, mediators of cell growth and vasculogenesis, and regulators of immune response. Our recent in vivo studies with mouse tumor models have confirmed that PDT treatment has a pronounced impact on sphingolipid profile in the targeted tumor and that significant advances in therapeutic gain with PDT can be attained by combining this modality with adjuvant treatment with ceramide analog LCL29.

  13. Dissolution of pre-existing platelet thrombus by synergistic administration of low concentrations of bifunctional antibodies against β3 integrin.

    Directory of Open Access Journals (Sweden)

    Suying Dang

    Full Text Available Most antithrombotic approaches target prevention rather than the more clinically relevant issue of resolution of an existing thrombus. In this study, we describe a novel and effective therapeutic strategy for ex vivo clearance of pre-existing platelet thrombus by the combination of two bifunctional platelet GPIIIa49-66 ligands that target different parts of the arterial thrombus. We produced an additional GPIIIa49-66 agent (named APAC, which homes to activated platelets. Like our previously described SLK (which targets newly deposited fibrin strands surrounding the platelet thrombus, APAC destroys platelet aggregates ex vivo in an identical fashion with 85% destruction of platelet aggregates at 2 hours. The combined application of APAC and SLK demonstrated a ~2 fold greater platelet thrombus dissolution than either agent alone at a low concentration (0.025 µM. Platelet-rich clot lysis experiments demonstrated the time required for 50% platelet-rich fibrin clot lysis (T(50% by APAC (95 ± 6.1 min or SLK (145 ± 7.1 min was much longer than that by combined APAC + SLK (65 ± 7.6 min at the final concentration of 0.025 µM (APAC + SLK vs APAC, p<0.05; APAC + SLK vs SLK, p<0.01. Thus these low concentrations of a combination of both agents are likely to be more effective and less toxic when used therapeutically in vivo.

  14. Heterogeneity of publicly accessible online critical values for therapeutic drugs

    Directory of Open Access Journals (Sweden)

    Colt M McClain

    2011-01-01

    Full Text Available Introduction: Critical values are reported to clinicians when laboratory values are life threatening and require immediate attention. To date no definitive critical value limit recommendations have been produced regarding therapeutic drug monitoring. Some laboratories choose to publish critical value lists online. These publicly available values may be accessed and potentially utilized by laboratory staff, patient care providers, and patients. Materials and Methods: A web-based search of laboratories associated with the Accreditation Council for Graduate Medical Education pathology residency programs was initiated to determine which therapeutic drugs had critical values and to examine the degree of variation in published critical values for these institutions. Results: Of the 107 institutions with university-based pathology training programs, 36 had published critical values online for review. Thirteen therapeutic drugs were investigated and the number of institutions reporting critical value limits for the drug, as well as the median, range, standard deviation, and the coefficient of variation of critical value concentration limits for each drug were determined. A number of the online critical value limits were deemed to be erroneous, most likely due to incorrectly listed units of measurement. Conclusions: There was a large degree of heterogeneity with regard to the chosen critical value limits for therapeutic drugs. This wide variance in critical values appears to be greater than that observed in interassay proficiency testing. Institutions should reexamine the rationale for their current critical value parameters and ensure that critical value limits and associated units are accurately published online.

  15. Using therapeutic assessment to explore emotional constriction: a creative professional in crisis

    NARCIS (Netherlands)

    Kamphuis, J.H.; de Saeger, H.; Finn, S.E.; Fischer, C.T.; Handler, L.

    2012-01-01

    A guide to conducting Collaborative/Therapeutic Assessment to promote client growth Mental health professionals are increasingly enthusiastic about and ready to use psychological test data, research, and theory in life-relevant ways to improve diagnosis, client care, and treatment outcomes. With

  16. Therapeutic drug monitoring of infliximab : performance evaluation of three commercial ELISA kits

    NARCIS (Netherlands)

    Schmitz, E.M.H.; van de Kerkhof, D.; Hamann, D.; van Dongen, J.L.J.; Kuijper, P.H.M.; Brunsveld, L.; Scharnhorst, V.; Broeren, M.A.C.

    2016-01-01

    BACKGROUND: Therapeutic drug monitoring (TDM) of infliximab (IFX, Remicade®) can aid to optimize therapy efficacy. Many assays are available for this purpose. However, a reference standard is lacking. Therefore, we evaluated the analytical performance, agreement and clinically relevant differences

  17. The value of non-human primates in the development of therapeutic monoclonal antibodies

    NARCIS (Netherlands)

    Van Meer, P.J.K.|info:eu-repo/dai/nl/34153790X; Kooijman, M.|info:eu-repo/dai/nl/322905788; Van Der Laan, J.W.|info:eu-repo/dai/nl/374879966; Moors, E.H.M.|info:eu-repo/dai/nl/20241664X; Schellekens, H.|info:eu-repo/dai/nl/068406762

    2011-01-01

    The pharmaceutical industry is increasingly focusing on the development of biological therapeutics. These molecules generally cause no off-target toxicity and are highly species specific. Therefore, non-human primates (NHPs) are often the only relevant species in which to conduct regulatory safety

  18. Spaceflight and Neurosurgery: A Comprehensive Review of the Relevant Literature.

    Science.gov (United States)

    Swinney, Christian C; Allison, Zain

    2018-01-01

    Spaceflight and the associated gravitational fluctuations may impact various components of the central nervous system. These include changes in intracranial pressure, the spine, and neurocognitive performance. The implications of altered astronaut performance on critical spaceflight missions are potentially significant. The current body of research on this important topic is extremely limited, and a comprehensive review has not been published. Herein, the authors address this notable gap, as well as the role of the neurosurgeon in optimizing potential diagnostic and therapeutic modalities. A literature search was conducted using the PubMed, EMBASE, and Google Scholar databases, with no time constraints. Significant manuscripts on physiologic changes associated with spaceflight and microgravity were identified and reviewed. Manifestations were separated into 1 of 3 general categories, including changes in intracranial pressure, the spine, and neurocognitive performance. A comprehensive literature review yielded 27 studies with direct relevance to the impact of microgravity and spaceflight on nervous system physiology. This included 7 studies related to intracranial pressure fluctuations, 17 related to changes in the spinal column, and 3 related to neurocognitive change. The microgravity environment encountered during spaceflight impacts intracranial physiology. This includes changes in intracranial pressure, the spinal column, and neurocognitive performance. Herein, we present a systematic review of the published literature on this issue. Neurosurgeons should have a key role in the continued study of this important topic, contributing to both diagnostic and therapeutic understanding. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Does relevance matter in academic policy research

    DEFF Research Database (Denmark)

    Dredge, Dianne

    2015-01-01

    A reflection on whether relevance matters in tourism policy research, and if so, to whom/what should it matter......A reflection on whether relevance matters in tourism policy research, and if so, to whom/what should it matter...

  20. Inoculating Relevance Feedback Against Poison Pills

    NARCIS (Netherlands)

    Dehghani, Mostafa; Azarbonyad, Hosein; Kamps, Jaap; Hiemstra, Djoerd; Marx, Maarten

    2016-01-01

    Relevance Feedback is a common approach for enriching queries, given a set of explicitly or implicitly judged documents to improve the performance of the retrieval. Although it has been shown that on average, the overall performance of retrieval will be improved after relevance feedback, for some

  1. Relevant cost information for order acceptance decisions

    NARCIS (Netherlands)

    Wouters, M.J.F.

    1997-01-01

    Some economic considerations for order acceptance decisions are discussed. The relevant economic considerations for order acceptance are widely discussed in the literature: only those costs are relevant which would be avoidable by not accepting the order incremental costs plus opportunity costs .

  2. Android Smartphone Relevance to Military Weather Applications

    Science.gov (United States)

    2011-10-01

    lithium -ion battery that may be replaced by the user (unlike Apple iPod Touch devices), thus spare batteries can be carried. If there is only sporadic...Android Smartphone Relevance to Military Weather Applications by David Sauter ARL-TR-5793 October 2011...Android Smartphone Relevance to Military Weather Applications David Sauter Computational and Information Sciences Directorate, ARL

  3. Using small XML elements to support relevance

    NARCIS (Netherlands)

    G. Ramirez Camps (Georgina); T.H.W. Westerveld (Thijs); A.P. de Vries (Arjen)

    2006-01-01

    htmlabstractSmall XML elements are often estimated relevant by the retrieval model but they are not desirable retrieval units. This paper presents a generic model that exploits the information obtained from small elements. We identify relationships between small and relevant elements and use this

  4. Translation as secondary communication. The relevance theory ...

    African Journals Online (AJOL)

    Ernst-August Gutt started one of the greatest translation debates of the past ten years when he suggested that relevance theory holds the key to providing a unified account of translation. The bulk of the debate has been between practitioners of functional equivalence and advocates of a relevance theoretic approach to ...

  5. Evolutionary relevance facilitates visual information processing.

    Science.gov (United States)

    Jackson, Russell E; Calvillo, Dusti P

    2013-11-03

    Visual search of the environment is a fundamental human behavior that perceptual load affects powerfully. Previously investigated means for overcoming the inhibitions of high perceptual load, however, generalize poorly to real-world human behavior. We hypothesized that humans would process evolutionarily relevant stimuli more efficiently than evolutionarily novel stimuli, and evolutionary relevance would mitigate the repercussions of high perceptual load during visual search. Animacy is a significant component to evolutionary relevance of visual stimuli because perceiving animate entities is time-sensitive in ways that pose significant evolutionary consequences. Participants completing a visual search task located evolutionarily relevant and animate objects fastest and with the least impact of high perceptual load. Evolutionarily novel and inanimate objects were located slowest and with the highest impact of perceptual load. Evolutionary relevance may importantly affect everyday visual information processing.

  6. Evolutionary Relevance Facilitates Visual Information Processing

    Directory of Open Access Journals (Sweden)

    Russell E. Jackson

    2013-07-01

    Full Text Available Visual search of the environment is a fundamental human behavior that perceptual load affects powerfully. Previously investigated means for overcoming the inhibitions of high perceptual load, however, generalize poorly to real-world human behavior. We hypothesized that humans would process evolutionarily relevant stimuli more efficiently than evolutionarily novel stimuli, and evolutionary relevance would mitigate the repercussions of high perceptual load during visual search. Animacy is a significant component to evolutionary relevance of visual stimuli because perceiving animate entities is time-sensitive in ways that pose significant evolutionary consequences. Participants completing a visual search task located evolutionarily relevant and animate objects fastest and with the least impact of high perceptual load. Evolutionarily novel and inanimate objects were located slowest and with the highest impact of perceptual load. Evolutionary relevance may importantly affect everyday visual information processing.

  7. Translational nanomedicine--through the therapeutic window.

    Science.gov (United States)

    Pierce, Robin L

    2015-01-01

    Translational nanomedicine occurs only through the successful integration of multiple inputs and iterative modifications. The therapeutic window plays a pivotal role in the trajectory of translational nanomedicine. Often defined in terms of the range of dosage for safe and effective therapeutic effect, a second definition of the therapeutic window refers to the often narrow temporal window in which a therapeutic effect can be obtained. Expanding the second definition to explicitly include the spatial dimension, this article explores aspects of the therapeutic spaces created by nanomedicine that shift the traditional dimensions of symptom, sign and pathology. This article analyzes three aspects of the therapeutic window in nanomedicine - temporal, spatial and manner of construction and their impact on the dimensions of modern medicine.

  8. Skewed Epigenetics: An Alternative Therapeutic Option for Diabetes Complications

    Directory of Open Access Journals (Sweden)

    Gabriele Togliatto

    2015-01-01

    Full Text Available Vascular complications are major causes of morbidity and mortality in type 2 diabetes patients. Mitochondrial reactive oxygen species (ROS generation and a lack of efficient antioxidant machinery, a result of hyperglycaemia, mainly contribute to this problem. Although advances in therapy have significantly reduced both morbidity and mortality in diabetic individuals, diabetes-associated vascular complications are still one of the most challenging health problems worldwide. New healing options are urgently needed as current therapeutics are failing to improve long-term outcomes. Particular effort has recently been devoted to understanding the functional relationship between chromatin structure regulation and the persistent change in gene expression which is driven by hyperglycaemia and which accounts for long-lasting diabetic complications. A detailed investigation into epigenetic chromatin modifications in type 2 diabetes is underway. This will be particularly useful in the design of mechanism-based therapeutics which interfere with long-lasting activating epigenetics and improve patient outcomes. We herein provide an overview of the most relevant mechanisms that account for hyperglycaemia-induced changes in chromatin structure; the most relevant mechanism is called “metabolic memory.”

  9. Therapeutic drug monitoring of isoniazid and rifampicin during anti-tuberculosis treatment in Auckland, New Zealand.

    Science.gov (United States)

    Maze, M J; Paynter, J; Chiu, W; Hu, R; Nisbet, M; Lewis, C

    2016-07-01

    There is uncertainty as to the optimal therapeutic concentrations of anti-tuberculosis drugs to achieve cure. To characterise the use of therapeutic drug monitoring (TDM), and identify risk factors and outcomes for those with concentrations below the drug interval. Patients treated for tuberculosis (TB) who had rifampicin (RMP) or isoniazid (INH) concentrations measured between 1 January 2005 and 31 December 2012 were studied retrospectively. Matched concentrations and drug dosing time were assessed according to contemporary regional drug intervals (RMP > 6 μmol/l, INH > 7.5 μmol/l) and current international recommendations (RMP > 10 μmol/l, INH > 22 μmol/l). Outcomes were assessed using World Health Organization criteria. Of 865 patients, 121 had concentrations of either or both medications. RMP concentrations were within the regional drug intervals in 106/114 (93%) and INH in 91/100 (91%). Concentrations were within international drug intervals for RMP in 76/114 (67%) and INH in 53/100 (53%). Low weight-based dose was the only statistically significant risk factor for concentrations below the drug interval. Of the 35 patients with low concentrations, 21 were cured, 9 completed treatment and 5 transferred out. There were no relapses during follow-up (mean 66.5 months). There were no clinically useful characteristics to guide use of TDM. Many patients had concentrations below international therapeutic intervals, but were successfully treated.

  10. COMPLEMENTARY APPROACHES TO THE DETERMINATION OF ARSENIC SPECIES RELEVANT TO CONCENTRATED ANIMAL FEEDING OPERATIONS

    Science.gov (United States)

    Ion-exchange chromatography is the most often used analytical approach for arsenicspeciation, due to the weak-acid nature of several of its species. However, no singletechnique can determine all potentially occurring arsenic species, especially in complexe...

  11. Comparison of extraction techniques for isolation of steroid oestrogens in environmentally relevant concentrations from sediment

    Czech Academy of Sciences Publication Activity Database

    Sadílek, Jan; Spálovská, P.; Vrana, B.; Vávrová, M.; Maršálek, Blahoslav; Šimek, Z.

    2016-01-01

    Roč. 96, č. 11 (2016), s. 1022-1037 ISSN 0306-7319 Institutional support: RVO:67985939 Keywords : microwave - assisted extraction * estrogens * sediment Subject RIV: CB - Analytical Chemistry , Separation Impact factor: 1.208, year: 2016

  12. Effects of Environmentally Relevant Concentrations of Bisphenol A on the Fathead Minnow

    Science.gov (United States)

    Bisphenol A (BPA) is a wide-spread environmental contaminant of concern due, in part, to possible effects on the vertebrate hypothalamic-pituitary-gonadal (HPG) axis, including activation of the estrogen receptor (ER). There is a reasonable amount of toxicological information fo...

  13. Metformin exposure at environmentally relevant concentrations causes potential endocrine disruption in adult male fish

    Science.gov (United States)

    Pharmaceuticals and personal care products (PPCPs) are emerging contaminants that have been found ubiquitously in wastewater and surface waters around the world. A major source of these compounds is incomplete metabolism in humans and subsequent excretion in human waste. PPCPs th...

  14. EXPOSURE TO ENVIRONMENTALLY RELEVANT CONCENTRATIONS OF DIFFERENT NONYLPHENOL FORMULATIONS IN JAPANESE MEDAKA. (R827098)

    Science.gov (United States)

    The time course of exposure to p-nonylphenol (NP) from two different sources was compared to equalivent exposures of 17--estradiol (E2) and a solvent control (ethanol; EtOH). Japanese medaka were exposed for 4 days to a nomina...

  15. Effect of ethanol at clinically relevant concentrations on atrial inward rectifier potassium current sensitive to acetylcholine

    Czech Academy of Sciences Publication Activity Database

    Bébarová, M.; Matejovič, P.; Pásek, Michal; Hořáková, Z.; Hošek, J.; Šimurdová, M.; Šimurda, J.

    2016-01-01

    Roč. 389, č. 10 (2016), s. 1049-1058 ISSN 0028-1298 Institutional support: RVO:61388998 Keywords : arrhythmias * atrial cardiomyocyte * inward rectifier potasssium current * ethanol * rat atrial cell model Subject RIV: BO - Biophysics Impact factor: 2.558, year: 2016

  16. Concentrations of undeclared allergens in food products can reach levels that are relevant for public health

    NARCIS (Netherlands)

    Spanjersberg, M. Q. I.; Knulst, A. C.; Kruizinga, A. G.; Van Duijn, G.; Houben, G. F.

    2010-01-01

    Food products can become contaminated with food allergens due to cross-contact. Precautionary 'may contain' labelling may alert to the possible presence of an allergen, but guidance for such labelling is lacking. As a result, allergy information on the packaging may not be reliable and allergic

  17. Detecting the effects of environmentally relevant concentrations of thyroid hormone disrupting compounds on amphibian development

    NARCIS (Netherlands)

    Gutleb, A.C.

    2006-01-01

    Persistent organic pollutants such as PCBs have been hypothesized to contribute to the observed global decline of amphibian populations. Thyroid hormone (TH) disruption is one of the possible mechanisms for effects of xenobiotics on amphibian development. In addition to the important functions

  18. Therapeutic cloning in individual parkinsonian mice

    Science.gov (United States)

    Tabar, Viviane; Tomishima, Mark; Panagiotakos, Georgia; Wakayama, Sayaka; Menon, Jayanthi; Chan, Bill; Mizutani, Eiji; Al-Shamy, George; Ohta, Hiroshi; Wakayama, Teruhiko; Studer, Lorenz

    2009-01-01

    Cell transplantation with embryonic stem (ES) cell progeny requires immunological compatibility with host tissue. ‘Therapeutic cloning’ is a strategy to overcome this limitation by generating nuclear transfer (nt)ES cells that are genetically matched to an individual. Here we establish the feasibility of treating individual mice via therapeutic cloning. Derivation of 187 ntES cell lines from 24 parkinsonian mice, dopaminergic differentiation, and transplantation into individually matched host mice showed therapeutic efficacy and lack of immunological response. PMID:18376409

  19. Therapeutic Sleep for Traumatic Brain Injury

    Science.gov (United States)

    2017-06-01

    AWARD NUMBER: W81XWH-16-1-0166 TITLE: Therapeutic Sleep for Traumatic Brain Injury PRINCIPAL INVESTIGATOR: Ravi Allada CONTRACTING...1. REPORT DATE June 2017 2. REPORT TYPE Annual 3. DATES COVERED 1June2016 - 31May2017 4. TITLE AND SUBTITLE Therapeutic Sleep for Traumatic Brain ...proposal will test the hypothesis that correcting sleep disorders can have a therapeutic effect onTraumatic Brain Injury (TBI) The majority of TBI

  20. Therapeutic potential of curcumin in gastrointestinal diseases

    OpenAIRE

    Rajasekaran, Sigrid A

    2011-01-01

    Curcumin, also known as diferuloylmethane, is derived from the plant Curcuma longa and is the active ingredient of the spice turmeric. The therapeutic activities of curcumin for a wide variety of diseases such as diabetes, allergies, arthritis and other chronic and inflammatory diseases have been known for a long time. More recently, curcumin’s therapeutic potential for preventing and treating various cancers is being recognized. As curcumin’s therapeutic promise is being explored more system...

  1. Dreams and Psychedelics: Neurophenomenological Comparison and Therapeutic Implications

    Science.gov (United States)

    Kraehenmann, Rainer

    2017-01-01

    Background: A resurgence of neurobiological and clinical research is currently underway into the therapeutic potential of serotonergic or ‘classical’ psychedelics such as the prototypical psychedelic drug lysergic acid diethylamide (LSD) psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) and ayahuasca – a betacarboline- and dimethyltryptamine (DMT)-containing Amazonian beverage. The aim of this review is to introduce readers to the similarities and dissimilarities between psychedelic states and night dreams and to draw conclusions related to therapeutic applications of psychedelics in psychiatry. Methods: Research literature related to psychedelics and dreaming is reviewed and these two states of consciousness are systematically compared. Relevant conclusions with regard to psychedelic-assisted therapy will be provided. Results: Common features between psychedelic states and night dreams include perception mental imagery emotion activation fear memory extinction and sense of self and body. Differences between these two states are related to differential perceptual input from the environment clarity of consciousness and meta-cognitive abilities. Therefore psychedelic states are closest to lucid dreaming which is characterized by a mixed state of dreaming and waking consciousness Conclusion: The broad overlap between dreaming and psychedelic states supports the notion that psychedelics acutely induce dreamlike subjective experiences which may have long-term beneficial effects on psychosocial functioning and well-being. Future clinical studies should examine how therapeutic outcome is related to the acute dreamlike effects of psychedelics. PMID:28625125

  2. Dreams and Psychedelics: Neurophenomenological Comparison and Therapeutic Implications.

    Science.gov (United States)

    Kraehenmann, Rainer

    2017-01-01

    A resurgence of neurobiological and clinical research is currently underway into the therapeutic potential of serotonergic or 'classical' psychedelics, such as the prototypical psychedelic drug lysergic acid diethylamide (LSD), psilocybin (4-phosphoryloxy-N,Ndimethyltryptamine), and ayahuasca - a betacarboline- and dimethyltryptamine (DMT)-containing Amazonian beverage. The aim of this review is to introduce readers to the similarities and dissimilarities between psychedelic states and night dreams, and to draw conclusions related to therapeutic applications of psychedelics in psychiatry. Research literature related to psychedelics and dreaming is reviewed, and these two states of consciousness are systematically compared. Relevant conclusions with regard to psychedelicassisted therapy will be provided. Common features between psychedelic states and night dreams include perception, mental imagery, emotion activation, fear memory extinction, and sense of self and body. Differences between these two states are related to differential perceptual input from the environment, clarity of consciousness and meta-cognitive abilities. Therefore, psychedelic states are closest to lucid dreaming which is characterized by a mixed state of dreaming and waking consciousness. The broad overlap between dreaming and psychedelic states supports the notion that psychedelics acutely induce dreamlike subjective experiences which may have long-term beneficial effects on psychosocial functioning and well-being. Future clinical studies should examine how therapeutic outcome is related to the acute dreamlike effects of psychedelics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Therapeutic targets in liver fibrosis.

    Science.gov (United States)

    Fallowfield, Jonathan A

    2011-05-01

    Detailed analysis of the cellular and molecular mechanisms that mediate liver fibrosis has provided a framework for therapeutic approaches to prevent, slow down, or even reverse fibrosis and cirrhosis. A pivotal event in the development of liver fibrosis is the activation of quiescent hepatic stellate cells (HSCs) to scar-forming myofibroblast-like cells. Consequently, HSCs and the factors that regulate HSC activation, proliferation, and function represent important antifibrotic targets. Drugs currently licensed in the US and Europe for other indications target HSC-related components of the fibrotic cascade. Their deployment in the near future looks likely. Ultimately, treatment strategies for liver fibrosis may vary on an individual basis according to etiology, risk of fibrosis progression, and the prevailing pathogenic milieu, meaning that a multiagent approach could be required. The field continues to develop rapidly and starts to identify exciting potential targets in proof-of-concept preclinical studies. Despite this, no antifibrotics are currently licensed for use in humans. With epidemiological predictions for the future prevalence of viral, obesity-related, and alcohol-related cirrhosis painting an increasingly gloomy picture, and a shortfall in donors for liver transplantation, the clinical urgency for new therapies is high. There is growing interest from stakeholders keen to exploit the market potential for antifibrotics. However, the design of future trials for agents in the developmental pipeline will depend on strategies that enable equal patient stratification, techniques to reliably monitor changes in fibrosis over time, and the definition of clinically meaningful end points.

  4. Therapeutic communities, old and new.

    Science.gov (United States)

    Jones, M

    1979-01-01

    The author attempts to clarify two largely different uses of term, Therapeutic Community (TC). By "old" TC he describes a movement which originated in psychiatry in the United Kingdom at the end of World War II. This was an attempt to establish a democratic system in hospitals where the domination of the doctors was replaced by open communication of content and feeling, information sharing, shared decision making, and problem solving shared as far as possible with all patients and staff. Daily meetings of all patients and staff formed the nucleus of this process. In recent years developments in the areas of systems theory, learning theory, and organization development have contributed to a better understanding of social organization and change. The "new" TCs derive from the more recent developments in the treatment of substance abuse. Central to this movement is Synanon and its many modification which use the clients' peer group to solve their own problems, largely eliminating mental health professionals. Linked with these "new" TCs is the development of Asklepieion units in prisons, which use Synanon "games" along with transactional analysis. An attempt is made to distinguish the methodologies used in TCs, "old" and "new".

  5. Therapeutic embolization in pulmonary hemorrhage

    International Nuclear Information System (INIS)

    Gasparini, D.

    1989-01-01

    The author's purpose was to evaluate the efficacy of therapeutic embolization in pulmonary hemorrage performed with fibrin foam (Spongostan) suspended in sclerosing agents (hidroxy-poliethoxy-dodecano 3%, or natrium morruate 5%), and electrocoagulation (Bitrol, spa) as an alternative to surgery. Twenty patients were embolized: 17 with fibrin foam and sclerosing agents only, 2 with the addition of electrocoagulation and a Gianturco coil respectively, and 1 with electrocoagulation alone. The follow-up ranges from 3 to 42 months (average 22). A patient affected by aspergilloma died a few days after hemoptysis. The patient treated by electrocoagulation alone suffers from periodical hematic expectoration (spitting). The remaining 18 patients have not shown any pathological findings. In 2 cases the arterial occlusion was confirmed by angiography, while in 1 case partial arterial recanalization was observed. Such a finding was due to the vessel dimensions and to hyperflux values. In similar cases, obstruction must be completed different techniques (e.g. Gianturco coils, electrocoagulation, detachable balloons, etc.). The absence of flux resulting from embolization improves electrocoagulation efficiency, which should be considered as the technique of choice. Even though additional trials are needed, the techniques have proven quite reliable and suitable to replace surgery in low-aggression lesions

  6. Prospects for therapeutic mitochondrial transplantation.

    Science.gov (United States)

    Gollihue, Jenna L; Rabchevsky, Alexander G

    2017-07-01

    Mitochondrial dysfunction has been implicated in a multitude of diseases and pathological conditions- the organelles that are essential for life can also be major players in contributing to cell death and disease. Because mitochondria are so well established in our existence, being present in all cell types except for red blood cells and having the responsibility of providing most of our energy needs for survival, then dysfunctional mitochondria can elicit devastating cellular pathologies that can be widespread across the entire organism. As such, the field of "mitochondrial medicine" is emerging in which disease states are being targeted therapeutically at the level of the mitochondrion, including specific antioxidants, bioenergetic substrate additions, and membrane uncoupling agents. New and compelling research investigating novel techniques for mitochondrial transplantation to replace damaged or dysfunctional mitochondria with exogenous healthy mitochondria has shown promising results, including tissue sparing accompanied by increased energy production and decreased oxidative damage. Various experimental techniques have been attempted and each has been challenged to accomplish successful transplantation. The purpose of this review is to present the history of mitochondrial transplantation, the different techniques used for both in vitro and in vivo delivery, along with caveats and pitfalls that have been discovered along the way. Results from such pioneering studies are promising and could be the next big wave of "mitochondrial medicine" once technical hurdles are overcome. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  7. Insulin resistance in therapeutic clinic

    Directory of Open Access Journals (Sweden)

    Anna V. Pashentseva

    2017-09-01

    Full Text Available Today an obesity became the global epidemic striking both children, and adults and represents one of the most important problems of health care worldwide. Excess accumulation of fatty tissue is resulted by insulin resistance and a compensatory hyperinsulinaemia which are the main predictors of development of a diabetes mellitus type 2. Insulin resistance is also one of key links of a pathogenesis of such diseases as cardiovascular pathology, not-alcoholic fatty liver disease, a polycystic ovary syndrome, gestational diabetes and many others. Depression of sensitivity of tissues to insulin can be physiological reaction of an organism to stress factors and pathological process. The endogenic reasons also take part in development of insulin resistance besides factors of the external environment. The role of genetic predisposition, a subclinical inflammation of fatty tissue, thyroid hormones, adipokines and vitamin D in formation of this pathological process is studied. As insulin resistance takes part in a pathogenesis of various diseases, methods of its diagnostics and correction are of great importance in therapeutic practice. At purpose of treatment it is worth giving preference to the drugs which are positively influencing sensitivity of tissues to insulin.

  8. Utility of a Bayesian Mathematical Model to Predict the Impact of Immunogenicity on Pharmacokinetics of Therapeutic Proteins.

    Science.gov (United States)

    Kathman, Steven; Thway, Theingi M; Zhou, Lei; Lee, Stephanie; Yu, Steven; Ma, Mark; Chirmule, Naren; Jawa, Vibha

    2016-03-01

    The impact of an anti-drug antibody (ADA) response on pharmacokinetic (PK) of a therapeutic protein (TP) requires an in-depth understanding of both PK parameters and ADA characteristics. The ADA and PK bioanalytical assays have technical limitations due to high circulating levels of TP and ADA, respectively, hence, significantly hindering the interpretation of this assessment. The goal of this study was to develop a population-based modeling and simulation approach that can identify a more relevant PK parameter associated with ADA-mediated clearance. The concentration-time data from a single dose PK study using five monoclonal antibodies were modeled using a non-compartmental analysis (NCA), one-compartmental, and two-compartmental Michaelis-Menten kinetic model (MMK). A novel PK parameter termed change in clearance time of the TP (α) derived from the MMK model could predict variations in α much earlier than the time points when ADA could be bioanalytically detectable. The model could also identify subjects that might have been potentially identified as false negative due to interference of TP with ADA detection. While NCA and one-compartment models can estimate loss of exposures, and changes in clearance, the two-compartment model provides this additional ability to predict that loss of exposure by means of α. Modeling data from this study showed that the two-compartment model along with the conventional modeling approaches can help predict the impact of ADA response in the absence of relevant ADA data.

  9. Astrophysical relevance of γ transition energies

    International Nuclear Information System (INIS)

    Rauscher, Thomas

    2008-01-01

    The relevant γ energy range is explicitly identified where additional γ strength must be located to have an impact on astrophysically relevant reactions. It is shown that folding the energy dependences of the transmission coefficients and the level density leads to maximal contributions for γ energies of 2≤E γ ≤4 unless quantum selection rules allow isolated states to contribute. Under this condition, electric dipole transitions dominate. These findings allow us to more accurately judge the relevance of modifications of the γ strength for astrophysics

  10. Neutrophil programming dynamics and its disease relevance.

    Science.gov (United States)

    Ran, Taojing; Geng, Shuo; Li, Liwu

    2017-11-01

    Neutrophils are traditionally considered as first responders to infection and provide antimicrobial host defense. However, recent advances indicate that neutrophils are also critically involved in the modulation of host immune environments by dynamically adopting distinct functional states. Functionally diverse neutrophil subsets are increasingly recognized as critical components mediating host pathophysiology. Despite its emerging significance, molecular mechanisms as well as functional relevance of dynamically programmed neutrophils remain to be better defined. The increasing complexity of neutrophil functions may require integrative studies that address programming dynamics of neutrophils and their pathophysiological relevance. This review aims to provide an update on the emerging topics of neutrophil programming dynamics as well as their functional relevance in diseases.

  11. Pediatric health, medicine, and therapeutics

    Directory of Open Access Journals (Sweden)

    Claire E Wainwright

    2011-03-01

    Full Text Available Claire E Wainwright1,21Royal Children’s Hospital, Brisbane and Queensland, Queensland, Australia; 2Queensland Children’s Medical Research Institute, The University of Queensland, Brisbane, AustraliaThe idea of children as small adults with health care needs that can be managed by extrapolation from adult studies has now largely been abandoned. We now recognize that adult health and disease are closely linked to childhood factors and the critical and ethical importance of clinical research in pediatrics is increasingly being recognized.  While funding and output from pediatric clinical research continues to lag behind health research in adults, particularly in the area of therapeutics, the last decade has thankfully seen a dramatic increase in the number of pediatric studies and particularly randomized controlled clinical trials (RCTs. Since the 1997 Food and Drug Administration (FDA Modernization Act in the United States (US and the subsequent changes in drug registration regulatory systems in the US and Europe, there has been a huge increase in the number of pediatric studies sponsored by pharmaceutical companies. In the United Kingdom, the Medicine for Children’s Research Network was established in 2005 to address the lack of clinical studies in pediatrics. Over the first five years they reported an exciting increase in the number of high quality clinical studies and on their website they have a current portfolio of over 200 pediatric studies, half of which are RCTs and half are sponsored by pharmaceutical companies. Other countries particularly across Europe are also establishing similar programs. 

  12. Therapeutic strategies in pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Leonello eFuso

    2011-04-01

    Full Text Available Pulmonary hypertension (PH is a life-threatening condition characterized by elevated pulmonary arterial pressure. It is clinically classified into five groups: patients in the first group are considered to have pulmonary arterial hypertension (PAH whereas patients of the other groups have PH that is due to cardiopulmonary or other systemic diseases. The management of patients with PH has advanced rapidly over the last decade and the introduction of specific treatments especially for PAH has lead to an improved outcome. However, despite the progress in the treatment, the functional limitation and the survival of these patients remain unsatisfactory and there is no cure for PAH. Therefore the search for an ideal therapy still goes on. At present, two levels of treatment can be identified: primary and specific therapy. Primary therapy is directed at the underlying cause of the PH. It also includes a supportive therapy consisting in oxygen supplementation, diuretics, and anticoagulation which should be considered in all patients with PH. Specific therapy is directed at the PH itself and includes treatment with vasodilatators such as calcium channel blockers and with vasodilatator and pathogenetic drugs such as prostanoids, endothelin receptor antagonists and phosphodiesterase type-5 inhibitors. These drugs act in several pathogenetic mechanisms of the PH and are specific for PAH although they might be used also in the other groups of PH. Finally, atrial septostomy and lung transplantation are reserved for patients refractory to medical therapy. Different therapeutic approaches can be considered in the management of patients with PH. Therapy can be established on the basis of both the clinical classification and the functional class. It is also possible to adopt a goal-oriented therapy in which the timing of treatment escalation is determined by inadequate response to known prognostic indicators.

  13. Ultra flat ideal concentrators of high concentration

    Energy Technology Data Exchange (ETDEWEB)

    Chaves, Julio [IST, Physics Dept., Lisboa (Portugal); INETI-DER, Lisboa (Portugal); Collares-Pereira, Manuel [INETI-DER, Lisboa (Portugal)

    2000-07-01

    A new method for the design of nonimaging devices is presented. Its application to the design of ultra flat compact concentrators is analysed. These new concentrators are based on a combination of two stages: the first one is composed of a large number of small structures placed side by side and the second one is a very compact single device concentrating the radiation to the limit. These devices are ideal for 2D. These compact designs are much more compact than the traditional ones like lens-mirror combinations or parabolic primaries with nonimaging secondaries. Besides, they can be designed for any acceptance angle, while the traditional ones are limited to small acceptance angles. (Author)

  14. Highly concentrating Fresnel lenses

    International Nuclear Information System (INIS)

    Kritchman, E.M.; Friesem, A.A.; Yekutieli, G.

    1979-01-01

    A new type of concave Fresnel lens capable of concentrating solar radiation very near the ultimate concentration limit is considered. The differential equations that describe the lens are solved to provide computed solutions which are then checked by ray tracing techniques. The performance (efficiency and concentration) of the lens is investigated and compared to that of a flat Fresnel lens, showing that the new lens is preferable for concentrating solar radiation. (author)

  15. Solar cell concentrating system

    International Nuclear Information System (INIS)

    Garg, H.P.; Sharma, V.K.; Agarwal, R.K.

    1986-11-01

    This study reviews fabrication techniques and testing facilities for different solar cells under concentration which have been developed and tested. It is also aimed to examine solar energy concentrators which are prospective candidates for photovoltaic concentrator systems. This may provide an impetus to the scientists working in the area of solar cell technology

  16. Rheology of concentrated biomass

    Science.gov (United States)

    J.R. Samaniuk; J. Wang; T.W. Root; C.T. Scott; D.J. Klingenberg

    2011-01-01

    Economic processing of lignocellulosic biomass requires handling the biomass at high solids concentration. This creates challenges because concentrated biomass behaves as a Bingham-like material with large yield stresses. Here we employ torque rheometry to measure the rheological properties of concentrated lignocellulosic biomass (corn stover). Yield stresses obtained...

  17. The foundation of the concept of relevance

    DEFF Research Database (Denmark)

    Hjørland, Birger

    2010-01-01

    that what was regarded as the most fundamental view by Saracevic in 1975 has not since been considered (with very few exceptions). Other views, which are based on less fruitful assumptions, have dominated the discourse on relevance in information retrieval and information science. Many authors have...... reexamined the concept of relevance in information science, but have neglected the subject knowledge view, hence basic theoretical assumptions seem not to have been properly addressed. It is as urgent now as it was in 1975 seriously to consider “the subject knowledge view” of relevance (which may also...... be termed “the epistemological view”). The concept of relevance, like other basic concepts, is influenced by overall approaches to information science, such as the cognitive view and the domain-analytic view. There is today a trend toward a social paradigm for information science. This paper offers...

  18. Exploring Educational Quality and Relevance through Integrating ...

    African Journals Online (AJOL)

    Exploring Educational Quality and Relevance through Integrating Environmental and Social Issues in Science Education. ... However, the new contextualised concept of learning and teaching was applied only to one of them. A post-test was ...

  19. Has Financial Statement Information become Less Relevant?

    DEFF Research Database (Denmark)

    Thinggaard, Frank; Damkier, Jesper

    This paper presents insights into the question of whether accounting information based on the EU’s Accounting Directives has become less value-relevant to investors over time. The study is based on a research design first used by Francis and Schipper (1999), where value-relevance is measured......? The sample is based on non-financial companies listed on the Copenhagen Stock Exchange in the period 1984-2002. Our analyses show that all the applied accounting measures are value-relevant as investment strategies based on the information earn positive market-adjusted returns in our sample period....... The results provide some indication of a decline in the value-relevance of earnings information in the 1984-2001 period, and mixed, but not statistically reliable, evidence for accounting measures where book value information and asset values are also extracted from financial statements. The results seem...

  20. [A therapeutic education tool in paediatric dentistry].

    Science.gov (United States)

    Marquillier, Thomas; Trentesaux, Thomas; Catteau, Céline; Delfosse, Caroline

    Therapeutic education for children is developing in the treatment of dental caries. The Elmy pathway, a pedagogical game aiming to improve children's oral health skills, has been designed. The qualitative assessment of this tool seems to confirm its benefit for use in therapeutic education sessions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. Woodland in Practical Skills Therapeutic Education

    Science.gov (United States)

    Mata, Paula; Gibons, Kenneth; Mata, Fernando

    2016-01-01

    Modern urban life provides less opportunities to contact with nature, which is a potential cause of developmental deviances in children. We investigated the potential therapeutic effect of woodlands, within the context of Practical Skills Therapeutic Education at the Ruskin Mill College, UK. Data on physical and emotional perceptions were…

  2. Translational nanomedicine : Through the therapeutic window

    NARCIS (Netherlands)

    Pierce, Robin

    2015-01-01

    Translational nanomedicine occurs only through the successful integration of multiple inputs and iterative modifications. The therapeutic window plays a pivotal role in the trajectory of translational nanomedicine. Often defined in terms of the range of dosage for safe and effective therapeutic

  3. Biological, clinical and population relevance of 95 loci for blood lipids

    NARCIS (Netherlands)

    T.M. Teslovich (Tanya); K. Musunuru (Kiran); A.V. Smith (Albert Vernon); A.C. Edmondson (Andrew); I.M. Stylianou (Ioannis); M. Koseki (Masahiro); J.P. Pirruccello (James); S. Ripatti (Samuli); D.I. Chasman (Daniel); C.J. Willer (Cristen); C.T. Johansen (Christopher); S.W. Fouchier (Sigrid); A.J. Isaacs (Aaron); G.M. Peloso (Gina); M. Barbalic (maja); S.L. Ricketts (Sally); J.C. Bis (Joshua); Y.S. Aulchenko (Yurii); G. Thorleifsson (Gudmar); M.F. Feitosa (Mary Furlan); J. Chambers (John); M. Orho-Melander (Marju); O. Melander (Olle); T. Johnson (Toby); X. Li (Xiaohui); X. Guo (Xiuqing); Y. Shin Cho (Yoon); M. Jin Go (Min); Y. Jin Kim (Young); J.Y. Lee (Jong Young); T. Park (Taesung); Y-J. Kim (Yong-Jin); X. Sim (Xueling); R. Twee-Hee Ong (Rick); D.C. Croteau-Chonka (Damien); L.A. Lange (Leslie); K. Song (Kijoung); J.H. Zhao (Jing Hua); X. Yuan (Xin); J. Luan; C. Lamina (Claudia); A. Ziegler (Andreas); W. Zhang (Weibo); R.Y.L. Zee (Robert); A.F. Wright (Alan); J.C.M. Witteman (Jacqueline); J.F. Wilson (James); G.A.H.M. Willemsen (Gonneke); H.E. Wichmann (Heinz Erich); J. Whitfield (John); D. Waterworth (Dawn); N.J. Wareham (Nick); G. Waeber (Gérard); P. Vollenweider (Peter); B.F. Voight (Benjamin); V. Vitart (Veronique); A.G. Uitterlinden (André); M. Uda (Manuela); J. Tuomilehto (Jaakko); J.R. Thompson (John); T. Tanaka (Toshiko); I. Surakka (Ida); H.M. Stringham (Heather); T.D. Spector (Timothy); N. Soranzo (Nicole); J.H. Smit (Johannes); J. Sinisalo (Juha); K. Silander (Kaisa); E.J.G. Sijbrands (Eric); A. Scuteri (Angelo); J. Scott (James); D. Schlessinger (David); S. Sanna (Serena); V. Salomaa (Veikko); J. Saharinen (Juha); C. Sabatti (Chiara); A. Ruokonen (Aimo); I. Rudan (Igor); L.M. Rose (Lynda); R. Roberts (Robert); M. Rieder (Mark); B.M. Psaty (Bruce); P.P. Pramstaller (Peter Paul); I. Pichler (Irene); M. Perola (Markus); B.W.J.H. Penninx (Brenda); N.L. Pedersen (Nancy); C. Pattaro (Cristian); A.N. Parker (Alex); G. Pare (Guillaume); B.A. Oostra (Ben); M.S. Nieminen (Markku); D.A. Nickerson (Deborah); G.W. Montgomery (Grant); T. Meitinger (Thomas); R. McPherson (Ruth); M.I. McCarthy (Mark); W.L. McArdle (Wendy); D. Masson (David); N.G. Martin (Nicholas); F. Marroni (Fabio); M. Mangino (Massimo); P.K. Magnusson (Patrik); G. Lucas (Gavin); R.N. Luben (Robert); R.J.F. Loos (Ruth); M.L. Lokki; G. Lettre (Guillaume); C. Langenberg (Claudia); L.J. Launer (Lenore); E. Lakatta (Edward); R. Laaksonen (Reijo); K.O. Kyvik (Kirsten Ohm); F. Kronenberg (Florian); I.R. König (Inke); K-T. Khaw (Kay-Tee); J. Kaprio (Jaakko); R.C. Kaplan (Robert); A. Johansson (Åsa); M.-R. Jarvelin (Marjo-Riitta); A. Cecile (A.); E. Ingelsson (Erik); W. Igl (Wilmar); G. Kees Hovingh; J.J. Hottenga (Jouke Jan); A. Hofman (Albert); A.A. Hicks (Andrew); C. Hengstenberg (Christian); I.M. Heid (Iris); C. Hayward (Caroline); A.S. Havulinna (Aki); N. Hastie (Nick); T.B. Harris (Tamara); T. Haritunians (Talin); A.S. Hall (Alistair); U. Gyllensten (Ulf); C. Guiducci (Candace); L. Groop (Leif); E. Gonzalez (Elena); C. Gieger (Christian); N.B. Freimer (Nelson); L. Ferrucci (Luigi); J. Erdmann (Jeanette); P. Elliott (Paul); K.G. Ejebe (Kenechi); A. Döring (Angela); A. Dominiczak (Anna); S. Demissie (Serkalem); P. Deloukas (Panagiotis); E.J.C. de Geus (Eco); U. de Faire (Ulf); G. Crawford (Gabe); F.S. Collins (Francis); C. Chen (Chao); M. Caulfield (Mark); H. Campbell (Harry); N.P. Burtt (Noël); L.L. Bonnycastle (Lori); D.I. Boomsma (Dorret); S.M. Boekholdt (Matthijs); R.N. Bergman (Richard); I.E. Barroso (Inês); S. Bandinelli (Stefania); C. Ballantyne (Christie); T.L. Assimes (Themistocles); T. Quertermous (Thomas); D. Altshuler (David); M. Seielstad (Mark); T.Y. Wong (Tien Yin); E.S. Tai (Shyong); A.B. Feranil (Alan); C.W. Kuzawa (Christopher); L.S. Adair (Linda); H.A. Taylor (Herman); I.B. Borecki (Ingrid); S.B. Gabriel (Stacey); H. Holm (Hilma); U. Thorsteinsdottir (Unnur); V. Gudnason (Vilmundur); R.M. Krauss (Ronald); K.L. Mohlke (Karen); J.M. Ordovas (Jose); P. Munroe (Patricia); J.S. Kooner (Jaspal); A.R. Tall (Alan); R.A. Hegele (Robert); J.J.P. Kastelein (John); E.E. Schadt (Eric); J.I. Rotter (Jerome); E.A. Boerwinkle (Eric); D.P. Strachan (David); V. Mooser (Vincent); J-A. Zwart (John-Anker); M.P. Reilly (Muredach); N.J. Samani (Nilesh); H. Schunkert (Heribert); L.A. Cupples (Adrienne); M.S. Sandhu (Manjinder); P.M. Ridker (Paul); D.J. Rader (Daniel); P. Tikka-Kleemola (Päivi); L. Peltonen (Leena Johanna); G.R. Abecasis (Gonçalo); M. Boehnke (Michael); S. Kathiresan (Sekar); C.J. O'Donnell (Christopher)

    2010-01-01

    textabstractPlasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for

  4. Correlation between paclitaxel Tc > 0.05 and its therapeutic efficacy and severe toxicities in ovarian cancer patients

    Directory of Open Access Journals (Sweden)

    Shuyao Zhang

    2016-01-01

    Conclusion: These results indicated that the PTX Tc > 0.05 correlated with therapeutic efficacy and drug toxicity. Therefore, monitoring the PTX Tc > 0.05 other than blood concentration of PTX is necessary to optimize individual treatment.

  5. [Enduring relevance. An introduction to the clinical contributions of K. R. Eissler].

    Science.gov (United States)

    Garcia, Emanuel E

    2007-01-01

    The author offers a personal selection and discussion of papers that epitomize the enduring relevance of Eissler's contributions to psychoanalytic therapy. The innovations of technique embodied by these works (on parameters, schizophrenia, adolescence, cure, fees, and the treatment of the dying patient) reveal a therapeutic approach that is a natural extension of psychoanalytic science: patient-centered, maximally comprehensive and appropriately flexible. Firsthand observations of Eissler's clinical manner and a selected bibliography are also presented.

  6. The effects of therapeutic touch on pain.

    Science.gov (United States)

    Monroe, Carolyn Magdalen

    2009-06-01

    To better understand how Therapeutic Touch can be used in today's health care arena, this integrative literature review will examine current research that will help answer the question, Does Therapeutic Touch reduce pain? An extensive search was conducted of the online databases MEDLINE, CINAHL, Cochrane Library, EMBASE, PsychLIT, and PubMed to retrieve research articles published from 1997 to 2007. Seven studies that were conducted between 1997 and 2004 were found and only five of the seven were included as pertinent evidence to answer the question. All of the research that was reviewed to answer whether Therapeutic Touch could significantly reduce pain revealed a majority of statistically significant positive results for implementing this intervention. Because there are no identified risks to Therapeutic Touch as a pain relief measure, it is safe to recommend despite the limitations of current research. Therapeutic Touch should be considered among the many possible nursing interventions for the treatment of pain.

  7. [Health security--GMOs in therapeutics].

    Science.gov (United States)

    Trouvin, J-H

    2003-03-01

    The recent progress in human therapeutics has been made possible thanks to molecular biology and its use in producing proteins having the same sequence and structure as that of human proteins. The use of GMOs allows production of proteins with high added value in therapeutics, which are of satisfactory quality. GMOs may also be directly administered to patients as gene therapy vectors. However, the use of GMOs in therapeutics must take into consideration some risks, particularly those of microbiological contamination, of neo-antigenicity as well as environmental risks with regard to the way of use of the GMO. Nevertheless, those risks are taken in due consideration in the development of these new medicinal products; solutions have been found to allow their use in therapeutics with a very positive benefit/risk ratio. Medicinal products from biotechnology have enabled considerable therapeutic progress without compromising health security.

  8. Therapeutic drug management of linezolid: a missed opportunity for clinicians?

    Science.gov (United States)

    Cattaneo, Dario; Gervasoni, Cristina; Cozzi, Valeria; Castoldi, Simone; Baldelli, Sara; Clementi, Emilio

    2016-12-01

    Some studies have shown that adjustments to the linezolid dose guided by therapeutic drug monitoring (TDM) can reduce interindividual variability in drug exposure and improve linezolid tolerability. In this study, 6 years of linezolid TDM, a diagnostic service for our hospital and others in the Milan (Italy) area, is described. Samples were collected immediately before the morning dose intake (trough concentrations) in steady-state conditions. Linezolid concentrations were quantified by a validated high-performance liquid chromatography (HPLC) method. Four hundred linezolid trough concentrations from 220 patients were collected. A 20-fold variability in linezolid levels was observed. Positive and significant correlations between linezolid trough concentrations and patient age (r = 0.325, P linezolid concentrations with time was observed in a subgroup of patients with more than one TDM assessment. Elderly patients, especially those aged >80 years and with impaired renal function, are at a higher risk of overexposure to linezolid. Despite the observed progressive increase in linezolid concentrations over time, most physicians did not change the drug dose according to the TDM results, even in the presence of frank overexposure to linezolid. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  9. Therapeutic Effect of Platelet-Rich Plasma in Rat Spinal Cord Injuries

    Directory of Open Access Journals (Sweden)

    Nan-Fu Chen

    2018-04-01

    Full Text Available Platelet-rich plasma (PRP is prepared by centrifuging fresh blood in an anticoagulant state, and harvesting the platelet-rich portion or condensing platelets. Studies have consistently demonstrated that PRP concentrates are an abundant source of growth factors, such as platelet-derived growth factor (PDGF, transforming growth factor β (TGF-β, insulin-like growth factor 1 (IGF-1, and epithelial growth factor (EGF. The complex mechanisms underlying spinal cord injury (SCI diminish intrinsic repair and neuronal regeneration. Several studies have suggested that growth factor-promoted axonal regeneration can occur for an extended period after injury. More importantly, the delivery of exogenous growth factors contained in PRP, such as EGF, IGF-1, and TGF-β, has neurotrophic effects on central nervous system (CNS injuries and neurodegenerative diseases. However, only a few studies have investigated the effects of PRP on CNS injuries or neurodegenerative diseases. According to our review of relevant literature, no study has investigated the effect of intrathecal (i.t. PRP injection into the injured spinal cord and activation of intrinsic mechanisms. In the present study, we directly injected i.t. PRP into rat spinal cords and examined the effects of PRP on normal and injured spinal cords. In rats with normal spinal cords, PRP induced microglia and astrocyte activation and PDGF-B and ICAM-1 expression. In rats with SCIs, i.t. PRP enhanced the locomotor recovery and spared white matter, promoted angiogenesis and neuronal regeneration, and modulated blood vessel size. Furthermore, a sustained treatment (a bolus of PRP followed by a 1/3 dose of initial PRP concentration exerted more favorable therapeutic effects than a single dose of PRP. Our findings suggest by i.t. PRP stimulate angiogenesis, enhancing neuronal regeneration after SCI in rats. Although PRP induces minor inflammation in normal and injured spinal cords, it has many advantages. It is an

  10. Post-therapeutic imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Pollice, Saverio, E-mail: saveriopollice@hotmail.it [Department of Radiology and Neuroradiology, “L. Bonomo Hospital”, 76123 Andria, BT (Italy); Muto, Mario, E-mail: mutomar@tiscali.it [Department of Neuroradiology, “Cardarelli Hospital”, Naples (Italy); Scarabino, Tommaso, E-mail: tscarabino@hotmail.com [Department of Radiology and Neuroradiology, “L. Bonomo Hospital”, 76123 Andria, BT (Italy)

    2015-05-15

    Highlights: • This study is the result of collaboration between neuroradiologists and neurosurgeons. • Comparison between neuroimaging techniques to better evaluate the complications after treatment of the spin. • Evaluation of the imaging features of complications and definition of follow-up. - Abstract: Any surgical approach modifies the normal anatomical and functional arrangement of the segmental spine which is aimed, therefore image interpretation cannot ignore a correct set of knowledge in the field of anatomy, pathophysiology, drug compliance, interventional radiology and surgery. Neuroradiological imaging has an important role before surgery to direct the surgeon or interventional radiologist during the operation, both in post-surgery, where imaging examination can rightly evaluate properties and effects of the treatment and can detect potential complications as infections, abscess, bleeding, exuberant scar, mobilization and rupture of devices. The available methods of imaging are the X-rays (XR) made at least in two projections, Computed Tomography (CT) with MPR (multiplanar) and VR (volume rendering) reconstruction, and Magnetic Resonance (MR), often performed before and after contrast media injection. Imaging assessment of spine after surgery is complex and depends upon several factors, including surgical procedures and disease for which it was performed; biomechanical of the underlying cortical and cancellous bone findings; conditions of muscles, intervertebral disk and ligaments; time since surgery procedures; duration and nature of the post-surgical syndrome. Depending upon several factors, one or a combination of complementary imaging modalities (X-rays, Computed Tomography, Magnetic Resonance) may be required to evaluate effectiveness of the treatment; to demonstrate any clinically relevant abnormality at the treated region and adjacent structures (complications such as inflammation, abscesses, bleeding and misplacement of the device); to

  11. Post-therapeutic imaging findings

    International Nuclear Information System (INIS)

    Pollice, Saverio; Muto, Mario; Scarabino, Tommaso

    2015-01-01

    Highlights: • This study is the result of collaboration between neuroradiologists and neurosurgeons. • Comparison between neuroimaging techniques to better evaluate the complications after treatment of the spin. • Evaluation of the imaging features of complications and definition of follow-up. - Abstract: Any surgical approach modifies the normal anatomical and functional arrangement of the segmental spine which is aimed, therefore image interpretation cannot ignore a correct set of knowledge in the field of anatomy, pathophysiology, drug compliance, interventional radiology and surgery. Neuroradiological imaging has an important role before surgery to direct the surgeon or interventional radiologist during the operation, both in post-surgery, where imaging examination can rightly evaluate properties and effects of the treatment and can detect potential complications as infections, abscess, bleeding, exuberant scar, mobilization and rupture of devices. The available methods of imaging are the X-rays (XR) made at least in two projections, Computed Tomography (CT) with MPR (multiplanar) and VR (volume rendering) reconstruction, and Magnetic Resonance (MR), often performed before and after contrast media injection. Imaging assessment of spine after surgery is complex and depends upon several factors, including surgical procedures and disease for which it was performed; biomechanical of the underlying cortical and cancellous bone findings; conditions of muscles, intervertebral disk and ligaments; time since surgery procedures; duration and nature of the post-surgical syndrome. Depending upon several factors, one or a combination of complementary imaging modalities (X-rays, Computed Tomography, Magnetic Resonance) may be required to evaluate effectiveness of the treatment; to demonstrate any clinically relevant abnormality at the treated region and adjacent structures (complications such as inflammation, abscesses, bleeding and misplacement of the device); to

  12. Effect of Therapeutic Touch in Patients with Cancer: a Literature Review.

    Science.gov (United States)

    Tabatabaee, Amir; Tafreshi, Mansoureh Zagheri; Rassouli, Maryam; Aledavood, Seyed Amir; AlaviMajd, Hamid; Farahmand, Seyed Kazem

    2016-04-01

    The use of complementary and alternative medicine (CAM) techniques has been growing. The National Center for Complementary and Alternative Medicine places therapeutic touch (TT) into the category of bio field energy. This literature review is aimed at critically evaluating the data from clinical trials examining the clinical efficacy of therapeutic touch as a supportive care modality in adult patients with cancer. Electronic databases (PubMed, Scopus, Scholar Google, and Science Direct) were searched from the year 1990 to 2015 to locate potentially relevant peer-reviewed articles using the key words therapeutic touch, touch therapy, neoplasm, cancer, and CAM. Additionally, relevant journals and references of all the located articles were manually searched for other potentially relevant studies. The number of 334 articles was found on the basis of the key words, of which 17 articles related to the clinical trial were examined in accordance with the objectives of the study. A total of 6 articles were in the final dataset in which several examples of the positive effects of healing touch on pain, nausea, anxiety and fatigue, and life quality and also on biochemical parameters were observed. Based on the results of this study, an affirmation can be made regarding the use of TT, as a non-invasive intervention for improving the health status in patients with cancer. Moreover, therapeutic touch was proved to be a useful strategy for adult patients with cancer.

  13. The therapeutic value of glycolic acid peels in dermatology

    Directory of Open Access Journals (Sweden)

    Grover C

    2003-03-01

    Full Text Available Chemical peeling or chemexfoliation has become increasingly popular in recent years for treatment of a number of cosmetic skin problems. Topical glycolic acid in the concentration of 10-30% for 3-5 minutes at fortnightly intervals was investigated as a therapeutic peeling agent in 41 patients having acne (39%, melasma (36.5%, post inflammatory hyperpigmentation (12% and superficial scarring of varied etiology (12%. A final evaluation done at 16 weeks revealed that this modality is useful especially in superficial scarring and melasma, moderately successful in acne patients with no response in dermal pigmentation. No significant untoward effects were seen.

  14. Acetaminophen-cysteine adducts during therapeutic dosing and following overdose

    Directory of Open Access Journals (Sweden)

    Judge Bryan S

    2011-03-01

    Full Text Available Abstract Background Acetaminophen-cysteine adducts (APAP-CYS are a specific biomarker of acetaminophen exposure. APAP-CYS concentrations have been described in the setting of acute overdose, and a concentration >1.1 nmol/ml has been suggested as a marker of hepatic injury from acetaminophen overdose in patients with an ALT >1000 IU/L. However, the concentrations of APAP-CYS during therapeutic dosing, in cases of acetaminophen toxicity from repeated dosing and in cases of hepatic injury from non-acetaminophen hepatotoxins have not been well characterized. The objective of this study is to describe APAP-CYS concentrations in these clinical settings as well as to further characterize the concentrations observed following acetaminophen overdose. Methods Samples were collected during three clinical trials in which subjects received 4 g/day of acetaminophen and during an observational study of acetaminophen overdose patients. Trial 1 consisted of non-drinkers who received APAP for 10 days, Trial 2 consisted of moderate drinkers dosed for 10 days and Trial 3 included subjects who chronically abuse alcohol dosed for 5 days. Patients in the observational study were categorized by type of acetaminophen exposure (single or repeated. Serum APAP-CYS was measured using high pressure liquid chromatography with electrochemical detection. Results Trial 1 included 144 samples from 24 subjects; Trial 2 included 182 samples from 91 subjects and Trial 3 included 200 samples from 40 subjects. In addition, we collected samples from 19 subjects with acute acetaminophen ingestion, 7 subjects with repeated acetaminophen exposure and 4 subjects who ingested another hepatotoxin. The mean (SD peak APAP-CYS concentrations for the Trials were: Trial 1- 0.4 (0.20 nmol/ml, Trial 2- 0.1 (0.09 nmol/ml and Trial 3- 0.3 (0.12 nmol/ml. APAP-CYS concentrations varied substantially among the patients with acetaminophen toxicity (0.10 to 27.3 nmol/ml. No subject had detectable APAP

  15. Oncolytic Viruses: Therapeutics With an Identity Crisis

    Directory of Open Access Journals (Sweden)

    Caroline J. Breitbach

    2016-07-01

    Full Text Available Oncolytic viruses (OV are replicating viral therapeutics for the treatment of cancer and have been in laboratory development for about twenty years. Recently, the FDA approved Imlygic, a herpes virus based therapeutic for the treatment of melanoma and thus OVs have entered a new era where they are a weapon in the armament of the oncologist. OVs are unique therapeutics with multiple mechanisms of therapeutic activity. The exact path for their development and eventual uptake by pharmaceutical companies is somewhat clouded by an uncertain identity. Are they vaccines, tumour lysing therapeutics, inducers of innate immunity, gene therapy vectors, anti-vascular agents or all of the above? Should they be developed as stand-alone loco-regional therapeutics, systemically delivered tumour hunters or immune modulators best tested as combination therapeutics? We summarize data here supporting the idea, depending upon the virus, that OVs can be any or all of these things. Pursuing a “one-size fits all” approach is counter-productive to their clinical development and instead as a field we should build on the strengths of individual virus platforms.

  16. Prognostic Relevance of Immunohistochemical Subclassification of Diffuse Large B-Cell Lymphoma in Two Prospective Phase III Clinical Trials

    NARCIS (Netherlands)

    Rayman, Nazik; Lam, King H.; van der Holt, Bronno; Koss, Clara; Veldhuizen, Dennis; Budel, Leo M.; Mulder, Andries H.; Verdonck, Leo F.; Delwel, Ruud; de Jong, Daphne; van Imhoff, Gustaaf W.; Sonneveld, Pieter

    Purpose: Until now molecular biologic techniques have not been easily used in daily clinical practice to stratify patients for therapeutic purposes. Therefore, we have investigated the prognostic relevance of the immunohistochemical (IHC) germinal center B-cell (GCB) versus non-GCB diffuse large

  17. Protein nanoparticles for therapeutic protein delivery.

    Science.gov (United States)

    Herrera Estrada, L P; Champion, J A

    2015-06-01

    Therapeutic proteins can face substantial challenges to their activity, requiring protein modification or use of a delivery vehicle. Nanoparticles can significantly enhance delivery of encapsulated cargo, but traditional small molecule carriers have some limitations in their use for protein delivery. Nanoparticles made from protein have been proposed as alternative carriers and have benefits specific to therapeutic protein delivery. This review describes protein nanoparticles made by self-assembly, including protein cages, protein polymers, and charged or amphipathic peptides, and by desolvation. It presents particle fabrication and delivery characterization for a variety of therapeutic and model proteins, as well as comparison of the features of different protein nanoparticles.

  18. Passage relevance models for genomics search

    Directory of Open Access Journals (Sweden)

    Frieder Ophir

    2009-03-01

    Full Text Available Abstract We present a passage relevance model for integrating syntactic and semantic evidence of biomedical concepts and topics using a probabilistic graphical model. Component models of topics, concepts, terms, and document are represented as potential functions within a Markov Random Field. The probability of a passage being relevant to a biologist's information need is represented as the joint distribution across all potential functions. Relevance model feedback of top ranked passages is used to improve distributional estimates of query concepts and topics in context, and a dimensional indexing strategy is used for efficient aggregation of concept and term statistics. By integrating multiple sources of evidence including dependencies between topics, concepts, and terms, we seek to improve genomics literature passage retrieval precision. Using this model, we are able to demonstrate statistically significant improvements in retrieval precision using a large genomics literature corpus.

  19. Nuclear data for the production of therapeutic radionuclides. Summary report of third research coordination meeting

    International Nuclear Information System (INIS)

    Sublet, J.-Ch.; Capote Noy, R.

    2006-08-01

    A summary is given of the Third Research Coordination Meeting on Nuclear Data for the Production of Therapeutic Radionuclides. The new library of evaluated cross-section will cover reactor and accelerator production of therapeutic radionuclides to appropriate specific activities and purity, along with the relevant decay data. A few new reactions were added at this meeting. Technical discussions and the resulting work plan to conclude the data evaluation activities are summarized for every reaction path. Timescales and agreed actions to deliver the database and Technical Report are also given. (author)

  20. Scandinavian clinical practice guidelines for therapeutic hypothermia and post-resuscitation care after cardiac arrest

    DEFF Research Database (Denmark)

    Castrén, M; Silfvast, T; Rubertsson, S

    2009-01-01

    BACKGROUND AND AIM: Sudden cardiac arrest survivors suffer from ischaemic brain injury that may lead to poor neurological outcome and death. The reperfusion injury that occurs is associated with damaging biochemical reactions, which are suppressed by mild therapeutic hypothermia (MTH). In several...... of Anaesthesiology and Intensive Care Medicine (SSAI). METHODS: Relevant studies were identified after two consensus meetings of the SSAI Task Force on Therapeutic Hypothermia (SSAITFTH) and via literature search of the Cochrane Central Register of Controlled Trials and Medline. Evidence was assessed and consensus...

  1. Establishment of clinically relevant radioresistant cell lines and their characteristics

    International Nuclear Information System (INIS)

    Fukumoto, Manabu; Kuwahara, Yoshikazu; Suzuki, Masatoshi

    2014-01-01

    Although radiotherapy is one of the major therapeutic modalities for eradicating malignant tumors, the existence of radioresistant cells remains one of the most critical obstacles. Standard radiotherapy consists of fractionated radiation (FR) of 2-Gy X-rays once a day, 5 days a week, over 60 Gy in total. To understand the characteristics of radioresistant cells and to develop more effective radiotherapy, we have established novel radioresistant cell lines by long-term (> 5 years) exposure to moderate doses of fractionated X-rays. While all the parental human cancer cells ceased, their radioresistant derivatives continue to proliferate with daily exposure to 2-Gy FR for more than 30 days. We have coined those cells as 'clinically relevant radioresistant' (CRR) cells. Transplanted tumors into nude mice were also CRR, indicating that CRR cell lines are powerful tools to improve cancer radiotherapy. We have shown that the suppression of autophagic cell death but not apoptosis was mainly involved in cellular radioresistance. An inhibitor of the mTOR pathway which enhances autophagy was effective to overcome CRR tumors induced in nude mice. But the underlined mechanism was not through the inhibition of autophagy. Guanine nucleotide-binding protein 1 (GBP1) over expression was necessary for maintaining the CRR phenotype, but radioresistant cells were not necessarily cancer stem cells (CSCs). Targeting GBP1 positive cancer cells may be a more efficient method in conquering cancer than targeting CSCs. Slight but significant radioresistance was acquired by 0.5 Gy/12 hrs of long-term FR exposures to parental cells for more than 31 days in accordance with cyclinD1 over expression. This acquired radioresistance (ARR) was stably maintained in the tumor cells even on 31 days after the cessation of 0.5-Gy FR. Present observations give a mechanistic insight for ARR of tumor cells through long-term FR exposure, and provide novel therapeutic targets for radiosensitization

  2. Identity theory and personality theory: mutual relevance.

    Science.gov (United States)

    Stryker, Sheldon

    2007-12-01

    Some personality psychologists have found a structural symbolic interactionist frame and identity theory relevant to their work. This frame and theory, developed in sociology, are first reviewed. Emphasized in the review are a multiple identity conception of self, identities as internalized expectations derived from roles embedded in organized networks of social interaction, and a view of social structures as facilitators in bringing people into networks or constraints in keeping them out, subsequently, attention turns to a discussion of the mutual relevance of structural symbolic interactionism/identity theory and personality theory, looking to extensions of the current literature on these topics.

  3. Precision Medicine for Hypertension Management in Chronic Kidney Disease: Relevance of SPRINT for Therapeutic Targets in Nondiabetic Renal Disease.

    Science.gov (United States)

    Ruzicka, Marcel; Burns, Kevin D; Hiremath, Swapnil

    2017-05-01

    In this review we evaluate the literature to determine if lower blood pressure (BP) targets are beneficial for patients with nondiabetic chronic kidney disease (CKD). Modification of Diet in Renal Disease (MDRD), African American Study of Kidney Disease and Hypertension (AASK), and Ramipril Efficacy in Nephropathy-2 (REIN-2), designed to assess the benefit of lower BP on progression of nondiabetic CKD, generally came to the same negative conclusion. They were not designed and powered to assess an effect of lower BP on cardiovascular outcomes. The Systolic Blood Pressure Intervention Trial (SPRINT) was the first trial designed and powered to address this issue, and showed a clear benefit of a lower targeted and achieved BP. SPRINT did not show any renal benefits from lower BP, and it was not designed to assess this outcome, and it enrolled patients with less "renal risk" per se. A distinguishing feature of SPRINT compared with other large trials is that it highlighted the importance of precise BP measurement methods in defining targets in hypertension treatment. Accordingly, we propose that SPRINT is truly a "game-changing" clinical trial that sets the bar for management of hypertension in select patients with nondiabetic CKD. In these patients, systolic BP target depends critically on the BP measurement method: < 140 mm Hg when derived from 3 readings using a mercury sphygmomanometer after 5 minutes of rest, < 130 mm Hg when calculated from at a minimum of 3 readings using an automated oscillometric device, and < 120 mm Hg when taken using an automated oscillometric device after 5 minutes of unattended rest. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  4. Therapeutic relevance of HRCT findings from a pneumological viewpoint; Therapeutische Relevanz des HRCT-Befundes aus pneumologischer Sicht

    Energy Technology Data Exchange (ETDEWEB)

    Suchy, R. [Klinik Donaustauf, Zentrum fuer Pneumologie, Donaustauf (Germany); Pfeifer, M. [Klinik Donaustauf, Universitaetsklinikum Regensburg, Krankenhaus Barmherzige Brueder Regensburg, Donaustauf (Germany)

    2014-12-15

    The high-resolution computed tomography (HRCT) technique is an essential component in diagnosing interstitial lung disease (ILD) as it provides important and specialized information and a much greater accuracy than chest X-rays. It contributes to a narrowing down of the differential diagnoses and is also important for planning further invasive investigations, e.g. bronchoscopy, bronchoalveolar lavage, transbronchial lung biopsy and surgical lung biopsy, if needed. An accurate diagnosis of ILD is based on a multidisciplinary discussion involving pulmonologists, radiologists and pathologists experienced in the diagnosis of ILD. The therapy approaches of five different entities of ILD are shown as examples. In hypersensitivity pneumonitis the mainstay of treatment is complete avoidance of exposure to the provoking antigen. In cryptogenic organizing pneumonia most patients recover with corticosteroid therapy with prednisolone over a period of 6 months to 1 year. In cases of sarcoidosis therapy depends on organ involvement and functional impairment but there is no durable benefit to routine treatment of patients with acute pulmonary sarcoidosis, even among those with stage II or III chest radiographs. In general, patients with severe or progressive disease will require treatment. In idiopathic pulmonary fibrosis (IPF) a confident radiological diagnosis of definitive usual interstitial pneumonia (UIP) obviates the need for surgical lung biopsy. Other etiologies of a HRCT pattern of UIP, such as domestic and occupational environmental exposure, connective tissue disease and drug toxicity must be ruled out. In IPF antifibrotic therapy with pirfenidone (approval since 2011) or the triple tyrosine kinase inhibitor nintendanib (pending approval in 2015) can reduce disease progression but therapy with acetylcysteine alone or in combination with prednisolone and azathioprine failed to meet efficacy endpoints. In the management of scleroderma associated ILD rapid semiquantitative evaluation of the extent of the disease on HRCT > 20 % is useful for identifying patients who require treatment. (orig.) [German] Die hochaufloesende CT (''high-resolution CT'', HRCT) ist der Goldstandard der bildgebenden Diagnostik bei der Abklaerung interstitieller Lungenerkrankungen (ILD), wobei sie richtungsweisende Befunde, ggf. eine favorisierte Verdachtsdiagnose liefert und das differenzialdiagnostische Spektrum einengt. Ausserdem ist sie wichtig zur Planung der weiteren invasiven Abklaerung mittels Bronchoskopie, bronchoalveolaerer Lavage sowie transbronchialer und ggf. chirurgischer Lungenbiopsie. Die Diagnose hinsichtlich der vorliegenden ILD wird im Gesamtkontext saemtlicher erhobener Untersuchungsergebnisse interdisziplinaer im ILD-Board gestellt, welches aus erfahrenen Kollegen der Pneumologie, Radiologie und Pathologie besteht. Exemplarisch wird die Therapie 5 verschiedener Lungenfibrosen dargestellt: Bei der exogen allergischen Alveolitis (EAA) hat die strenge Allergenexpositionsprophylaxe oberste Prioritaet. Die kryptogen organisierende Pneumonie spricht in der Regel gut auf eine Prednisolontherapie an, wobei von einer Gesamttherapiedauer von 6 bis 12 Monaten auszugehen ist. Im Falle einer Sarkoidose wird die Therapie von der Organbeteiligung sowie der funktionellen Einschraenkung abhaengig gemacht, aber keine ''Kosmetik'' der CT-morphologischen Veraenderungen per se vorgenommen. Im Allgemeinen besteht eine Therapieindikation bei einer ernsthaften oder progredienten Erkrankung. Bei der idiopathischen Lungenfibrose (IPF) ersetzt das HRCT-Muster der definitiven ''usual interstitial pneumonia'' (UIP) die chirurgische Lungenbiopsie. Die Diagnose IPF kann allerdings erst nach sorgfaeltigem Ausschluss bekannter Ursachen gestellt werden (chronische EAA, Asbestose, Lungenbeteiligung im Rahmen einer Kollagenose bzw. rheumatologischen Grunderkrankung, Medikamententoxizitaet). Die IPF kann mit dem antifibrotisch wirksamen, seit 2011 zugelassenen Medikament Pirfenidon, nach der derzeit noch ausstehenden Zulassung (erwartet fuer 2015) auch mit dem Tyrosinkinaseinhibitor Nintedanib behandelt werden, wodurch die Progression der Erkrankung verlangsamt werden kann. Acetylcystein alleine oder in Kombination mit Prednisolon und Azathioprin hat sich als nicht wirksam erwiesen. Bei der Behandlung der Sklerodermie mit Lungenbeteiligung traegt ein abgeschaetztes Fibroseausmass von > 20 % im HRCT massgeblich zur Therapieentscheidung bei. (orig.)

  5. Constitutive cannabinoid 1 and mu opioid receptor activity in the ventral tegmental area: occurrence, function and therapeutic relevance

    NARCIS (Netherlands)

    Meye, F.J.

    2012-01-01

    Cannabinoid 1 receptors (CB1Rs) play a crucial role in regulating systems dedicated to processing rewards and emotions. It was known that in artificial systems, CB1Rs can exhibit activity that is independent of the typical agonist-driven form. However, it remained largely unclear whether this

  6. A biophysical approach to menadione membrane interactions: relevance for menadione-induced mitochondria dysfunction and related deleterious/therapeutic effects.

    Science.gov (United States)

    Monteiro, João P; Martins, André F; Nunes, Cláudia; Morais, Catarina M; Lúcio, Marlene; Reis, Salette; Pinheiro, Teresa J T; Geraldes, Carlos F G C; Oliveira, Paulo J; Jurado, Amália S

    2013-08-01

    Menadione (MEN), a polycyclic aromatic ketone, was shown to promote cell injury by imposing massive oxidative stress and has been proposed as a promising chemotherapeutic agent for the treatment of cancer diseases. The mechanisms underlying MEN-induced mitochondrial dysfunction and cell death are not yet fully understood. In this work, a systematic study was performed to unveil the effects of MEN on membrane lipid organization, using models mimicking mitochondrial membranes and native mitochondrial membranes. MEN was found to readily incorporate in membrane systems composed of a single phospholipid (phosphatidylcholine) or the lipids dioleoylphosphatidylcholine, dioleoylphosphatidylethanolamine and tetraoleoylcardiolipin at 1:1:1 molar ratio, as well as in mitochondrial membranes. Increased permeability in both membrane models, monitored by calcein release, seemed to correlate with the extent of MEN incorporation into membranes. MEN perturbed the physical properties of vesicles composed of dipalmitoylphosphatidylcholine or dipalmitoylphosphatidylethanolamine plus tetraoleoylcardiolipin (at 7:3 molar ratio), as reflected by the downshift of the lipid phase transition temperature and the emergence of a new transition peak in the mixed lipid system, detected by DSC. (31)P NMR studies revealed that MEN favored the formation of non-lamellar structures. Also, quenching studies with the fluorescent probes DPH and TMA-DPH showed that MEN distributed across the bilayer thickness in both model and native mitochondrial membranes. MEN's ability to promote alterations of membrane lipid organization was related with its reported mitochondrial toxicity and promotion of apoptosis, predictably involved in its anti-carcinogenic activity. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Human Growth Hormone Delivery with a Microneedle Transdermal System: Preclinical Formulation, Stability, Delivery and PK of Therapeutically Relevant Doses

    Directory of Open Access Journals (Sweden)

    Mahmoud Ameri

    2014-05-01

    Full Text Available This study evaluated the feasibility of coating formulated recombinant human growth hormone (rhGH on a titanium microneedle transdermal delivery system, Zosano Pharma (ZP-hGH, and assessed preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. rhGH liquid formulation was coated onto titanium microneedles by dip-coating and drying. The stability of coated rhGH was determined by size exclusion chromatography-high performance liquid chromatography (SEC-HPLC. Preclinical delivery and pharmacokinetic studies were conducted in female hairless guinea pigs (HGP using rhGH coated microneedle patches at 0.5 and 1 mg doses and compared to Norditropin® a commercially approved rhGH subcutaneous injection. Studies demonstrated successful rhGH formulation development and coating on microneedle arrays. The ZP-hGH patches remained stable at 40 °C for six months with no significant change in % aggregates. Pharmacokinetic studies showed that the rhGH-coated microneedle patches, delivered with high efficiency and the doses delivered indicated linearity with average Tmax of 30 min. The absolute bioavailability of the microneedle rhGH patches was similar to subcutaneous Norditropin® injections. These results suggest that ZP-transdermal microneedle patch delivery of rhGH is feasible and may offer an effective and patient-friendly alternative to currently marketed rhGH injectables.

  8. Human Growth Hormone Delivery with a Microneedle Transdermal System: Preclinical Formulation, Stability, Delivery and PK of Therapeutically Relevant Doses.

    Science.gov (United States)

    Ameri, Mahmoud; Kadkhodayan, Miryam; Nguyen, Joe; Bravo, Joseph A; Su, Rebeca; Chan, Kenneth; Samiee, Ahmad; Daddona, Peter E

    2014-05-15

    This study evaluated the feasibility of coating formulated recombinant human growth hormone (rhGH) on a titanium microneedle transdermal delivery system, Zosano Pharma (ZP)-hGH, and assessed preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. rhGH liquid formulation was coated onto titanium microneedles by dip-coating and drying. The stability of coated rhGH was determined by size exclusion chromatography-high performance liquid chromatography (SEC-HPLC). Preclinical delivery and pharmacokinetic studies were conducted in female hairless guinea pigs (HGP) using rhGH coated microneedle patches at 0.5 and 1 mg doses and compared to Norditropin® a commercially approved rhGH subcutaneous injection. Studies demonstrated successful rhGH formulation development and coating on microneedle arrays. The ZP-hGH patches remained stable at 40 °C for six months with no significant change in % aggregates. Pharmacokinetic studies showed that the rhGH-coated microneedle patches, delivered with high efficiency and the doses delivered indicated linearity with average Tmax of 30 min. The absolute bioavailability of the microneedle rhGH patches was similar to subcutaneous Norditropin® injections. These results suggest that ZP-transdermal microneedle patch delivery of rhGH is feasible and may offer an effective and patient-friendly alternative to currently marketed rhGH injectables.

  9. Investigations of relevance of the tumor marker neopterine for therapeutic decision and control of progress in mammary carcinoma

    International Nuclear Information System (INIS)

    Hacker, I; Lauterbach, H.; Kob, D.

    1989-01-01

    The value of serum neopterin as tumor marker was verified in 104 breast cancer patients. Based on the results the evaluation of neopterin cannot be recommended, neither for the decision of treatment after primary therapy nor for monitoring of the breast cancer. (author)

  10. [Online Counselling: The prospect of a therapeutic connection].

    Science.gov (United States)

    Giotakos, O; Papadomarkaki, E

    2016-01-01

    Over the last few years, Internet has become an integral part of daily life. An abundant source of information and a principal gateway of communication between individuals, Internet has been continuously gaining considerable ground as a tool of awareness and intervention in the area of public health. With regard to the field of mental health, Internet exhibits a credible potential in facilitating dialogue not only between experts and their beneficiaries but also between stakeholders. Moreover and with regard to various aspects of public concern, it can serve as a circulation portal of educational material between students and teachers. The advent of remote support services dates back in the decade of 1970-1980. In the present time, they consist of informative guides and self-help groups or online counselling. The latter is defined as the process in which both parties, namely the therapist and the client, are involved in an oral or written conciliation through means of an internet connection, videoconferencing, live chat or e-mail exchange. The benefits of this practice - accessibility, relocation, convenience, anonymity, facilitation of face-to-face psychotherapy and low cost - could make online counseling, in specific cases, the treatment of choice. While the usage of the World Wide Web seems promising for the rectification of mental health disorders, there is some debate among experts regarding the ethical aspect of practicing psychotherapy in an interactive digital environment. Issues such as technical expertise and the tackling of related problems, difficulties in the diagnostic process, interchange of verbal and nonverbal cues, crisis management, safeguarding the therapeutic alliance, protection of personal data, age restriction, keeping boundaries in relation to the setting, the time and the dynamics of the therapeutic relationship and, finally, training and supervisory process of online therapist, are some subjects of disagreement. Relevant research reveals

  11. Towards new therapeutic strategies in chondrosarcoma

    NARCIS (Netherlands)

    Schrage, Yvonne Maria

    2009-01-01

    This thesis presents the identification of new targets for therapeutic treatment of chondrosarcoma, tumours that are highly insensitive to conventional chemo- and radiation thearapy. A relatively new array technique to identify active kinases in chondrosarcoma cell cultures was used, which

  12. Therapeutic hypothermia reduces intestinal ischemia/reperfusion ...

    African Journals Online (AJOL)

    The detached intestinal epithelial cells in hypothermia group showed ... of apoptosis than those in normothermia group at 4 h (17.30 ± 2.56 vs. ... intestinal ischemia/reperfusion (IR) injury, which could be attenuated by therapeutic hypothermia.

  13. Unconscious emotional reasoning and the therapeutic misconception.

    Science.gov (United States)

    Charuvastra, A; Marder, S R

    2008-03-01

    The "therapeutic misconception" describes a process whereby research volunteers misinterpret the intentions of researchers and the nature of clinical research. This misinterpretation leads research volunteers to falsely attribute a therapeutic potential to clinical research, and compromises informed decision making, therefore compromising the ethical integrity of a clinical experiment. We review recent evidence from the neurobiology of social cognition to provide a novel framework for thinking about the therapeutic misconception. We argue that the neurobiology of social cognition should be considered in any ethical analysis of how people make decisions about participating in clinical trials. The neurobiology of social cognition also suggests how the complicated dynamics of the doctor-patient relationship may unavoidably interfere with the process of obtaining informed consent. Following this argument we suggest new ways to prevent or at least mitigate the therapeutic misconception.

  14. Therapeutic platelet reduction: Use in postsplenectomy thrombocytosis

    Directory of Open Access Journals (Sweden)

    Gita Negi

    2015-01-01

    Full Text Available Therapeutic platelet reduction is an effective modality for the reduction of platelet count in patients with treatment of extreme thrombocytosis resulting from a variety of primary and secondary causes of thrombocytosis, which may be associated with thrombotic or hemorrhagic complications of varying degrees. These cases when symptomatic fall into the ASFA Category II indication for therapeutic platelet apheresis procedure. Here, we report a case of postsplenectomy secondary thrombocytosis presenting with extremely high platelet counts and subsequent thrombosis in the shunt and successful treatment after therapeutic platelet reduction. The case is being presented to bring forth the fact that therapeutic platelet reduction is an easy procedure that gives quick and good results and also to bring to the attention of transfusion specialists an associated but as yet unreported procedural finding.

  15. Therapeutic potential of fecal microbiota transplantation

    NARCIS (Netherlands)

    Smits, Loek P.; Bouter, Kristien E. C.; de Vos, Willem M.; Borody, Thomas J.; Nieuwdorp, Max

    2013-01-01

    There has been growing interest in the use of fecal microbiota for the treatment of patients with chronic gastrointestinal infections and inflammatory bowel diseases. Lately, there has also been interest in its therapeutic potential for cardiometabolic, autoimmune, and other extraintestinal

  16. Therapeutic radionuclides: Making the right choice

    International Nuclear Information System (INIS)

    Srivastava, S.C.

    1996-01-01

    Recently, there has been a resurgence of interest in nuclear medicine therapeutic procedures. Using unsealed sources for therapy is not a new concept; it has been around since the beginnings of nuclear medicine. Treatment of thyroid disorders with radioiodine is a classic example. The availability of radionuclides with suitable therapeutic properties for specific applications, as well as methods for their selective targeting to diseased tissue have, however, remained the main obstacles for therapy to assume a more widespread role in nuclear medicine. Nonetheless, a number of new techniques that have recently emerged, (e.g., tumor therapy with radiolabeled monoclonal antibodies, treatment of metastatic bone pain, etc.) appear to have provided a substantial impetus to research on production of new therapeutic radionuclides. Although there are a number of new therapeutic approaches requiring specific radionuclides, only selected broad areas will be used as examples in this article

  17. Malignant mesothelioma: biology, diagnosis and therapeutic approaches

    Czech Academy of Sciences Publication Activity Database

    Tomasetti, M.; Amati, M.; Santarelli, L.; Alleva, R.; Neužil, Jiří

    2009-01-01

    Roč. 2, č. 2 (2009), s. 190-206 ISSN 1874-4672 Institutional research plan: CEZ:AV0Z50520514 Keywords : malignant mesothelioma * biology * diagnosis and therapeutic approaches Subject RIV: EB - Genetics ; Molecular Biology

  18. [Pharmacokinetic alterations in pregnancy and use of therapeutic drug monitoring].

    Science.gov (United States)

    Panchaud, Alice; Weisskopf, Etienne; Winterfeld, Ursula; Baud, David; Guidi, Monia; Eap, Chin B; Csajka, Chantal; Widmer, Nicolas

    2014-01-01

    Following the thalidomide tragedy, pharmacological research in pregnant women focused primarily on drug safety for the unborn child and remains only limited regarding the efficacy and safety of treatment for the mother. Significant physiological changes during pregnancy may yet affect the pharmacokinetics of drugs and thus compromise its efficacy and/or safety. Therapeutic drug monitoring (TDM) would maximize the potential effectiveness of treatments, while minimizing the potential risk of toxicity for the mother and the fetus. At present, because of the lack of concentration-response relationship studies in pregnant women, TDM can rely only on individual assessment (based on an effective concentration before pregnancy) and remains reserved only to unexpected situations such as signs of toxicity or unexplained inefficiency. © 2014 Société Française de Pharmacologie et de Thérapeutique.

  19. Effectiveness of therapeutic barium enema for diverticular hemorrhage.

    Science.gov (United States)

    Matsuura, Mizue; Inamori, Masahiko; Nakajima, Atsushi; Komiya, Yasuhiko; Inoh, Yumi; Kawasima, Keigo; Naitoh, Mai; Fujita, Yuji; Eduka, Akiko; Kanazawa, Noriyoshi; Uchiyama, Shiori; Tani, Rie; Kawana, Kennichi; Ohtani, Setsuya; Nagase, Hajime

    2015-05-14

    To evaluate the effectiveness of barium impaction therapy for patients with colonic diverticular bleeding. We reviewed the clinical charts of patients in whom therapeutic barium enema was performed for the control of diverticular bleeding between August 2010 and March 2012 at Yokohama Rosai Hospital. Twenty patients were included in the review, consisting of 14 men and 6 women. The median age of the patients was 73.5 years. The duration of the follow-up period ranged from 1 to 19 mo (median: 9.8 mo). Among the 20 patients were 11 patients who required the procedure for re-bleeding during hospitalization, 6 patients who required it for re-bleeding that developed after the patient left the hospital, and 3 patients who required the procedure for the prevention of re-bleeding. Barium (concentration: 150 w%/v%) was administered per the rectum, and the leading edge of the contrast medium was followed up to the cecum by fluoroscopy. After confirmation that the ascending colon and cecum were filled with barium, the enema tube was withdrawn, and the patient's position was changed every 20 min for 3 h. Twelve patients remained free of re-bleeding during the follow-up period (range: 1-19 mo) after the therapeutic barium enema, including 9 men and 3 women with a median age of 72.0 years. Re-bleeding occurred in 8 patients including 5 men and 3 women with a median age of 68.5 years: 4 developed early re-bleeding, defined as re-bleeding that occurs within one week after the procedure, and the remaining 4 developed late re-bleeding. The DFI (disease-free interval) decreased 0.4 for 12 mo. Only one patient developed a complication from therapeutic barium enema (colonic perforation). Therapeutic barium enema is effective for the control of diverticular hemorrhage in cases where the active bleeding site cannot be identified by colonoscopy.

  20. Unexplored therapeutic opportunities in the human genome

    DEFF Research Database (Denmark)

    Oprea, Tudor I; Bologa, Cristian G; Brunak, Søren

    2018-01-01

    A large proportion of biomedical research and the development of therapeutics is focused on a small fraction of the human genome. In a strategic effort to map the knowledge gaps around proteins encoded by the human genome and to promote the exploration of currently understudied, but potentially d...... as well as key drug target classes, including G protein-coupled receptors, protein kinases and ion channels, which illustrate the nature of the unexplored opportunities for biomedical research and therapeutic development....

  1. Nanoparticles for therapeutic and diagnostic applications

    OpenAIRE

    Chiu, Yin To

    2014-01-01

    Nanomedicine focuses on the development and engineering of novel and unique therapeutic and diagnostic agents that can overcome the challenges associated with using traditional modalities. Nanoparticles (NPs) in the size range between 1 and 1000 nm have many advantages for use in these applications, such as, low polydispersity, established characterization methodologies, and the ability to be loaded with therapeutics for diseases, conjugated to targeting ligands to enhance specificity, and co...

  2. Therapeutic Strategy for Chronic Headache in Children

    Directory of Open Access Journals (Sweden)

    H.O. Lezhenko

    2016-05-01

    Full Text Available The therapeutic efficacy of a combined homeopathic preparation Cefavora, which consists of alcoholic extracts of Ginkgo biloba, hawthorn (Crataegus and white mistletoe (Viscum album, has been studied in the treatment of chronic tension-type headache in children. It has been shown that alongside with elimination of headache manifestations, the use of homeopathic medicine has contributed to the normalization of adaptive mechanisms of autonomic regulation in children indicating its high therapeutic efficacy.

  3. [Usher syndrome: clinical features, diagnostic options, and therapeutic prospects].

    Science.gov (United States)

    Seeliger, M W; Fischer, M D; Pfister, M

    2009-06-01

    Usher syndrome denotes a clinically and genetically heterogeneous combination of retinitis pigmentosa and sensorineural deafness. The division into subtypes I, II, and III is based on the degree of hearing loss: Type I is characterized by deafness from birth together with ataxia and retarded motor development, type II by a stationary deafness of a moderate degree, and type III by a progressive deafness with adult onset. In Germany, Usher syndrome currently bears particular relevance because in January 2009 a new compulsory screening of auditory function in newborn infants was introduced. Consequently, it can be expected that a higher number of patients with Usher syndrome will be identified in early childhood and referred to ophthalmologists. The focus of this work is to introduce the typical clinical picture of Usher syndrome, summarize diagnostic options, and give an overview of therapeutic strategies.

  4. Molecular pathogenesis of hepatocellular carcinoma and impact of therapeutic advances

    Science.gov (United States)

    Dhanasekaran, Renumathy; Bandoh, Salome; Roberts, Lewis R.

    2016-01-01

    Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality and has an increasing incidence worldwide. HCC can be induced by multiple etiologies, is influenced by many risk factors, and has a complex pathogenesis. Furthermore, HCCs exhibit substantial heterogeneity, which compounds the difficulties in developing effective therapies against this highly lethal cancer. With advances in cancer biology and molecular and genetic profiling, a number of different mechanisms involved in the development and progression of HCC have been identified. Despite the advances in this area, the molecular pathogenesis of hepatocellular carcinoma is still not completely understood. This review aims to elaborate our current understanding of the most relevant genetic alterations and molecular pathways involved in the development and progression of HCC, and anticipate the potential impact of future advances on therapeutic drug development. PMID:27239288

  5. Fiber-coupled Luminescence Dosimetry in Therapeutic and Diagnostic Radiology

    DEFF Research Database (Denmark)

    Andersen, Claus Erik

    2011-01-01

    . Some crystalline phosphors, such as carbon-doped aluminium oxide (Al2O3:C) have the ability to store charge produced in the crystal during irradiation. The stored charge may later be released by fiber-guided laser light under emission of so-called optically stimulated luminescence (OSL). The OSL signal......Fiber-coupled luminescence dosimetry is an emerging technology with several potentially attractive features of relevance for uses in therapeutic and diagnostic radiology: direct water equivalence (i.e. no significant perturbation of the radiation field in a water phantom or a patient), sub......-mm detector size, high dynamic range (below a mGy to several Gy), microsecond time resolution, and absence of electrical wires or other electronics in the dosimeter probe head. Fiber-coupled luminescence dosimetry systems typically consist of one or more small samples of phosphor, e.g. a mg of plastic...

  6. Autophagy as a Therapeutic Target in Cardiovascular Disease

    Science.gov (United States)

    Nemchenko, Andriy; Chiong, Mario; Turer, Aslan; Lavandero, Sergio; Hill, Joseph A.

    2011-01-01

    The epidemic of heart failure continues apace, and development of novel therapies with clinical efficacy has lagged. Now, important insights into the molecular circuitry of cardiovascular autophagy have raised the prospect that this cellular pathway of protein quality control may be a target of clinical relevance. Whereas basal levels of autophagy are required for cell survival, excessive levels – or perhaps distinct forms of autophagic flux – contribute to disease pathogenesis. Our challenge will be to distinguish mechanisms that drive adaptive versus maladaptive autophagy and to manipulate those pathways for therapeutic gain. Recent evidence suggests this may be possible. Here, we review the fundamental biology of autophagy and its role in a variety of forms of cardiovascular disease. We discuss ways in which this evolutionarily conserved catabolic mechanism can be manipulated, discuss studies presently underway in heart disease, and provide our perspective on where this exciting field may lead in the future. PMID:21723289

  7. Novel therapeutics for gastro-esophageal reflux symptoms.

    Science.gov (United States)

    Zerbib, Frank; Simon, Mireille

    2012-09-01

    Approximately 20-30% of patients with gastro-esophageal reflux symptoms report inadequate symptom relief while on proton-pump inhibitor therapy. The mechanisms involved are failure of the antireflux barrier (transient lower esophageal sphincter relaxations), high proximal extent of the refluxate, esophageal hypersensitivity and impaired mucosal integrity. Persisting acid or nonacid reflux can be demonstrated in 40-50% of cases, suggesting that there is room for antireflux therapy in these patients. New antireflux compounds have been shown to decrease the occurrence of transient lower esophageal sphincter relaxations. The most promising classes of compounds are GABA type B agonists and metabotropic glutamate receptor 5 antagonists, which can reduce both reflux episodes and symptoms, but the development of these compounds has been abandoned for either safety issues or lack of efficacy. Esophageal hypersensitivity and impaired mucosal integrity may prove to be relevant therapeutic targets in the future.

  8. Does Reducing the Concentration of Bupivacaine When Performing Therapeutic Shoulder Joint Injections Impact the Clinical Outcome?

    Science.gov (United States)

    Fox, Michael G; Patrie, James T

    2016-04-01

    Mixtures of local anesthetics and steroids are routinely injected intraarticularly to temporarily relieve joint pain, even though local anesthetics have been reported to cause chondrocyte death in a dose- and time-dependent manner. This study aimed to determine if intraarticular injections of bupivacaine 0.5% and bupivacaine 0.25% would provide similar pain relief. All fluoroscopically guided glenohumeral joint injections performed using 2.5 mL of bupivacaine and 0.5 mL (20 mg) of triamcinolone acetonide over a 42-month period were included if a pain score was recorded before, 5-10 minutes after, and 1 week after injection. Pain reduction of more than 2 points was considered much improved clinically with pain reduction of more than 1 point considered the minimum clinically important difference (MCID) threshold. Statistically significant and much improved pain reduction was achieved using both bupivacaine 0.5% and 0.25% 5-10 minutes (-3.7 points; 95% CI, -3.4 to -4.0 points; p ≤ 0.001; and -3.3 points; 95% CI, -3.0 to -3.5 points; p ≤ 0.001) and 1 week (-2.5 points; 95% CI, -2.2 to -2.9 points; p ≤ 0.001; and -2.1 points; 95% CI, -1.8 to -2.3 points; p ≤ 0.001) after injection, respectively. Adjusting for age, sex, pain score before injection, and indication, the mean decrease in pain was greater in the bupivacaine 0.5% group by 0.30 points 5-10 minutes after injection (95% CI, -0.03 to 0.63 points; p = 0.08) and 0.46 points 1 week after injection (95% CI, 0.13-0.77 points; p = 0.01). Both bupivacaine 0.5% and bupivacaine 0.25% provide statistically significant and much improved pain relief 5-10 minutes and 1 week after intraarticular glenohumeral injections. Bupivacaine 0.5% provided greater pain relief than bupivacaine 0.25%, but the difference was less than 0.5 points and therefore did not meet the MCID threshold.

  9. Bible Translation And Relevance Theory | Deist | Stellenbosch ...

    African Journals Online (AJOL)

    Stellenbosch Papers in Linguistics Plus. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 22 (1992) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Bible Translation And Relevance Theory. F Deist ...

  10. Relevant Scatterers Characterization in SAR Images

    Science.gov (United States)

    Chaabouni, Houda; Datcu, Mihai

    2006-11-01

    Recognizing scenes in a single look meter resolution Synthetic Aperture Radar (SAR) images, requires the capability to identify relevant signal signatures in condition of variable image acquisition geometry, arbitrary objects poses and configurations. Among the methods to detect relevant scatterers in SAR images, we can mention the internal coherence. The SAR spectrum splitted in azimuth generates a series of images which preserve high coherence only for particular object scattering. The detection of relevant scatterers can be done by correlation study or Independent Component Analysis (ICA) methods. The present article deals with the state of the art for SAR internal correlation analysis and proposes further extensions using elements of inference based on information theory applied to complex valued signals. The set of azimuth looks images is analyzed using mutual information measures and an equivalent channel capacity is derived. The localization of the "target" requires analysis in a small image window, thus resulting in imprecise estimation of the second order statistics of the signal. For a better precision, a Hausdorff measure is introduced. The method is applied to detect and characterize relevant objects in urban areas.

  11. Seeking Relevance: American Political Science and America

    Science.gov (United States)

    Maranto, Robert; Woessner, Matthew C.

    2012-01-01

    In this article, the authors talk about the relevance of American political science and America. Political science has enormous strengths in its highly talented practitioners and sophisticated methods. However, its disconnection from its host society, while not so severe as for fields like English and sociology, nonetheless poses an existential…

  12. Is Enterprise Education Relevant to Social Enterprise?

    Science.gov (United States)

    Bridge, Simon

    2015-01-01

    Purpose: Both enterprise education and social enterprise have become fashionable but what, if any, should be the connections between them? The purpose of this paper is to explore those connections and to reflect on what relevance the two concepts might have for each other. Design/methodology/approach: Both enterprise education and social…

  13. The Relevant Physical Trace in Criminal Investigation

    Directory of Open Access Journals (Sweden)

    Durdica Hazard

    2016-01-01

    Full Text Available A criminal investigation requires the forensic scientist to search and to interpret vestiges of a criminal act that happened in the past. The forensic scientist is one of the many stakeholders who take part in the information quest within the criminal justice system. She reads the investigation scene in search of physical traces that should enable her to tell the story of the offense/crime that allegedly occurred. The challenge for any investigator is to detect and recognize relevant physical traces in order to provide clues for investigation and intelligence purposes, and that will constitute sound and relevant evidence for the court. This article shows how important it is to consider the relevancy of physical traces from the beginning of the investigation and what might influence the evaluation process. The exchange and management of information between the investigation stakeholders are important. Relevancy is a dimension that needs to be understood from the standpoints of law enforcement personnel and forensic scientists with the aim of strengthening investigation and ultimately the overall judicial process.

  14. Interpersonal communication: It's relevance to nursing practice ...

    African Journals Online (AJOL)

    This paper is aimed at highlighting how essential interpersonal communication is necessary for establishing rapport, understanding the needs of the patients and planning effective intervention for meeting holistic health care. To be continually relevant, Nurses have to improve on their communication skills to meet the ...

  15. Inferring feature relevances from metric learning

    DEFF Research Database (Denmark)

    Schulz, Alexander; Mokbel, Bassam; Biehl, Michael

    2015-01-01

    Powerful metric learning algorithms have been proposed in the last years which do not only greatly enhance the accuracy of distance-based classifiers and nearest neighbor database retrieval, but which also enable the interpretability of these operations by assigning explicit relevance weights...

  16. The Relevance of Causal Social Construction

    Directory of Open Access Journals (Sweden)

    Marques Teresa

    2017-02-01

    Full Text Available Social constructionist claims are surprising and interesting when they entail that presumably natural kinds are in fact socially constructed. The claims are interesting because of their theoretical and political importance. Authors like Díaz-León argue that constitutive social construction is more relevant for achieving social justice than causal social construction. This paper challenges this claim. Assuming there are socially salient groups that are discriminated against, the paper presents a dilemma: if there were no constitutively constructed social kinds, the causes of the discrimination of existing social groups would have to be addressed, and understanding causal social construction would be relevant to achieve social justice. On the other hand, not all possible constitutively socially constructed kinds are actual social kinds. If an existing social group is constitutively constructed as a social kind K, the fact that it actually exists as a K has social causes. Again, causal social construction is relevant. The paper argues that (i for any actual social kind X, if X is constitutively socially constructed as K, then it is also causally socially constructed; and (ii causal social construction is at least as relevant as constitutive social construction for concerns of social justice. For illustration, I draw upon two phenomena that are presumed to contribute towards the discrimination of women: (i the poor performance effects of stereotype threat, and (ii the silencing effects of gendered language use.

  17. The economic lot size and relevant costs

    NARCIS (Netherlands)

    Corbeij, M.H.; Jansen, R.A.; Grübström, R.W.; Hinterhuber, H.H.; Lundquist, J.

    1993-01-01

    In many accounting textbooks it is strongly argued that decisions should always be evaluated on relevant costs; that is variable costs and opportunity costs. Surprisingly, when it comes to Economic Order Quantities or Lot Sizes, some textbooks appear to be less straightforward. The question whether

  18. Bootstrapping Visual Categorization with Relevant Negatives

    NARCIS (Netherlands)

    Li, X.; Snoek, C.G.M.; Worring, M.; Koelma, D.; Smeulders, A.W.M.

    Learning classifiers for many visual concepts are important for image categorization and retrieval. As a classifier tends to misclassify negative examples which are visually similar to positive ones, inclusion of such misclassified and thus relevant negatives should be stressed during learning.

  19. Why ritual plant use has ethnopharmacological relevance

    NARCIS (Netherlands)

    Quiroz, Diana; Sosef, Marc; Andel, Van Tinde

    2016-01-01

    Ethnopharmacological relevance Although ritual plant use is now recognised both for its socio-cultural importance and for its contribution to nature conservation, its potential pharmacological effects remain overlooked. Aim of the study Our objective was to see whether ritual plant use could have

  20. Bradford's Law and Its Relevance to Researchers

    Science.gov (United States)

    Shenton, Andrew K.; Hay-Gibson, Naomi V.

    2009-01-01

    Bradford's Law has been the subject of much discussion and analysis in library and information science since its formulation in the 1930s and remains frequently debated to this day. It has been applied to various practices within the discipline, especially with regard to collection development, but its relevance to researchers and the potential it…

  1. The relevance of cosmopolitanism for moral education

    NARCIS (Netherlands)

    Merry, M.S.; de Ruyter, D.J.

    2011-01-01

    In this article we defend a moral conception of cosmopolitanism and its relevance for moral education. Our moral conception of cosmopolitanism presumes that persons possess an inherent dignity in the Kantian sense and therefore they should be recognised as ends-in-themselves. We argue that

  2. Ranking Music Data by Relevance and Importance

    DEFF Research Database (Denmark)

    Ruxanda, Maria Magdalena; Nanopoulos, Alexandros; Jensen, Christian Søndergaard

    2008-01-01

    Due to the rapidly increasing availability of audio files on the Web, it is relevant to augment search engines with advanced audio search functionality. In this context, the ranking of the retrieved music is an important issue. This paper proposes a music ranking method capable of flexibly fusing...

  3. Fast multi-output relevance vector regression

    OpenAIRE

    Ha, Youngmin

    2017-01-01

    This paper aims to decrease the time complexity of multi-output relevance vector regression from O(VM^3) to O(V^3+M^3), where V is the number of output dimensions, M is the number of basis functions, and V

  4. Pragmatic inferences and self-relevant judgments

    DEFF Research Database (Denmark)

    Puente-Diaz, Rogelio; Cavazos Arroyo, Judith; Brem, Alexander

    2016-01-01

    Three studies examined the influence of type of scale on self-relevant judgments and the moderating role of age, prevention, focus, and need for cogni- tion. Participants were randomly assigned to a bipolar or a unipolar scale condition in all three studies. Results from study 1 with a representa...

  5. Making Chemistry Relevant to the Engineering Major

    Science.gov (United States)

    Basu-Dutt, Sharmistha; Slappey, Charles; Bartley, Julie K.

    2010-01-01

    As part of a campus-wide, externally funded project to increase performance in, enthusiasm for, and retention within STEM disciplines, we developed an interdisciplinary, team-taught first-year seminar course. The construction and delivery of this course was designed to show the relevance of selected general chemistry topics such as matter and…

  6. Contingent Attentional Capture by Conceptually Relevant Images

    Science.gov (United States)

    Wyble, Brad; Folk, Charles; Potter, Mary C.

    2013-01-01

    Attentional capture is an unintentional shift of visuospatial attention to the location of a distractor that is either highly salient, or relevant to the current task set. The latter situation is referred to as contingent capture, in that the effect is contingent on a match between characteristics of the stimuli and the task-defined…

  7. The Relevance Aura of Bibliographic Records.

    Science.gov (United States)

    Brooks, Terrence A.

    1997-01-01

    Analyzes relevance assessments of topical descriptors for bibliographic records for two dimensions: (1) a vertical conceptual hierarchy of broad to narrow descriptors, and (2) a horizontal linkage of related terms. The data were analyzed for a semantic distance and semantic direction effect as postulated by the Semantic Distance Model. (Author/LRW)

  8. The Relevance of Cosmopolitanism for Moral Education

    Science.gov (United States)

    Merry, Michael S.; de Ruyter, Doret J.

    2011-01-01

    In this article we defend a moral conception of cosmopolitanism and its relevance for moral education. Our moral conception of cosmopolitanism presumes that persons possess an inherent dignity in the Kantian sense and therefore they should be recognised as ends-in-themselves. We argue that cosmopolitan ideals can inspire moral educators to awaken…

  9. Concentration of stable elements in food products

    International Nuclear Information System (INIS)

    Montford, M.A.; Shank, K.E.; Hendricks, C.; Oakes, T.W.

    1980-01-01

    Food samples were taken from commercial markets and analyzed for stable element content. The concentrations of most stable elements (Ag, Al, As, Au, Ba, Br, Ca, Ce, Cl, Co, Cr, Cs, Cu, Fe, Hf, I, K, La, Mg, Mn, Mo, Na, Rb, Sb, Sc, Se, Sr, Ta, Th, Ti, V, Zn, Zr) were determined using multiple-element neutron activation analysis, while the concentrations of other elements (Cd, Hg, Ni, Pb) were determined using atomic absorption. The relevance of the concentrations found are noted in relation to other literature values. An earlier study was extended to include the determination of the concentration of stable elements in home-grown products in the vicinity of the Oak Ridge National Laboratory. Comparisons between the commercial and local food-stuff values are discussed

  10. Attention-driven auditory cortex short-term plasticity helps segregate relevant sounds from noise

    OpenAIRE

    Ahveninen, Jyrki; Hämäläinen, Matti; Jääskeläinen, Iiro P.; Ahlfors, Seppo P.; Huang, Samantha; Lin, Fa-Hsuan; Raij, Tommi; Sams, Mikko; Vasios, Christos E.; Belliveau, John W.

    2011-01-01

    How can we concentrate on relevant sounds in noisy environments? A “gain model” suggests that auditory attention simply amplifies relevant and suppresses irrelevant afferent inputs. However, it is unclear whether this suffices when attended and ignored features overlap to stimulate the same neuronal receptive fields. A “tuning model” suggests that, in addition to gain, attention modulates feature selectivity of auditory neurons. We recorded magnetoencephalography, EEG, and functional MRI (fMR...

  11. Chronically ill patients’ expectations of therapeutic education and their health locus of control

    Directory of Open Access Journals (Sweden)

    Małgorzata Anna Basińska

    2015-12-01

    Full Text Available Background Beliefs as cognitive components of personality indicate what we consider as true or false and help us to answer questions concerning others, the world surrounding us and situations that we encounter. Beliefs about the health locus of control and their relations with expectations pertaining to therapeutic education seem to be of vital importance in the case of occurrence of a chronic illness. The aim of this paper is to verify whether expectations concerning therapeutic education in chronically ill patients demonstrate a relation with beliefs about the health locus of control and whether they vary according to gender, age and health, and to present the results of research that applies the Polish OE-15 scale for the evaluation of therapeutic education expectations depending on the health condition. Participants and procedure Two hundred and ninety-one persons were examined, including 180 patients and 111 healthy controls (the control group, 187 women and 104 men. The average age of subjects was 45.71 (SD = 13.51 years, ranging from 21 to 80 years. The OE-15 Therapeutic Education Expectations Scale and the Multidimensional Health Locus of Control Scale in versions relevant for patients and healthy controls as well as demographics were used. Results Age, gender and beliefs about the health locus of control are related to expectations of therapeutic education. Conclusions When providing therapeutic education for chronically ill patients, one should assess their expectations and pay attention to patients’ beliefs about the health locus of control.

  12. Concentration - dose - risk computer code

    International Nuclear Information System (INIS)

    Frujinoiu, C.; Preda, M.

    1997-01-01

    Generally, the society is less willing in promoting remedial actions in case of low level chronic exposure situations. Radon in dwellings and workplaces is a case connected to chronic exposure. Apart from radon, the solely source on which the international community agreed for setting action levels, there are other numerous sources technically modified by man that can generate chronic exposure. Even if the nuclear installations are the most relevant, we are surrounded by 'man-made radioactivity' such as: mining industry, coal-fired power plants and fertilizer industry. The operating of an installation even within 'normal limits' could generate chronic exposure due to accumulation of the pollutants after a definite time. This asymptotic proclivity to a constant level define a steady-state concentration that represents a characteristic of the source's presence in the environment. The paper presents a methodology and a code package that derives sequentially the steady-state concentration, doses, detriments, as well as the costs of the effects of installation operation in a given environment. (authors)

  13. Interactions between Therapeutic Proteins and Acrylic Acid Leachable.

    Science.gov (United States)

    Liu, Dengfeng; Nashed-Samuel, Yasser; Bondarenko, Pavel V; Brems, David N; Ren, Da

    2012-01-01

    Leachables are chemical compounds that migrate from manufacturing equipment, primary containers and closure systems, and packaging components into biopharmaceutical and pharmaceutical products. Acrylic acid (at concentration around 5 μg/mL) was detected as leachable in syringes from one of the potential vendors (X syringes). In order to evaluate the potential impact of acrylic acid on therapeutic proteins, an IgG 2 molecule was filled into a sterilized X syringe and then incubated at 45 °C for 45 days in a pH 5 acetate buffer. We discovered that acrylic acid can interact with proteins at three different sites: (1) the lysine side chain, (2) the N-terminus, and (3) the histidine side chain, by the Michael reaction. In this report, the direct interactions between acrylic acid leachable and a biopharmaceutical product were demonstrated and the reaction mechanism was proposed. Even thought a small amount (from 0.02% to 0.3%) of protein was found to be modified by acrylic acid, the modified protein can potentially be harmful due to the toxicity of acrylic acid. After being modified by acrylic acid, the properties of the therapeutic protein may change due to charge and hydrophobicity variations. Acrylic acid was detected to migrate from syringes (Vendor X) into a therapeutic protein solution (at a concentration around 5 μg/mL). In this study, we discovered that acrylic acid can modify proteins at three different sites: (1) the lysine side chain, 2) the N-terminus, and 3) the histidine side chain, by the Michael reaction. In this report, the direct interactions between acrylic acid leachable and a biopharmaceutical product were demonstrated and the reaction mechanism was proposed.

  14. Hemorrhagic fever with renal syndrome: clinical, pathogenetic and therapeutic aspects

    Directory of Open Access Journals (Sweden)

    Vera F. Pavelkina

    2017-09-01

    Full Text Available Introduction: The republic of Mordovia (RM is an active natural focus of hemorrhagic fever with renal syndrome (HFRS. The incidence of HFRS ranges from 10 to 40 cases per 100 000 people, i.e. exceeds the average Russian rate. The relevance of HFRS is determined by the involvement of many organs and systems in the pathological process. The intoxication syndrome (IS takes a leading place in the pathogenesis of the disease. The development of IS is associated with both the phenomenon of viremia, and the accumulation of endogenous toxins in the body. Despite the large number of recommendations, the problem of IS correction is not completely solved. Antiviral drugs are not applicable in connection with a short period of viremia. Therefore, the basis of treatment is pathogenetic therapy. The purpose of research is to study the clinical, epidemiological and therapeutic aspects of the medium degree HFRS. Materials and Methods: In the course of the study, the patients of two groups were examined: the first group (comparison group, 35 patients received basal therapy; the second group (primary group, 25 patients received a dropwise preparation of remaxol (400 ml for 7 days intravenously. The control group consisted of 30 healthy people of a similar age group. The clinical features of the disease in the Republic of Mordovia, as well as objective indicators were observed. Urea, creatinine, alanine aminotransferase (ALT, aspartate aminotransferase (AST, medium-weight molecules (MWM, circulating immune complexes (CIC, total, effective concentration and binding capacity of albumin (TCA, ECA, BCA, and toxicity index (TI were studied. Results: The infection was mainly in rural areas (78.3 %. Despite the c yclicity of the course, there was no clearly defined period of oliguria in the HFRS clinic (in 22 %, polyuria in 27 % of cases. Hepatomegaly is combined with a change in functional liver samples. The pathological changes indicate the presence of IS, which

  15. Therapeutic Alliances in Stroke Rehabilitation: A Meta-Ethnography.

    Science.gov (United States)

    Lawton, Michelle; Haddock, Gillian; Conroy, Paul; Sage, Karen

    2016-11-01

    To synthesize qualitative studies exploring patients' and professionals' perspectives and experiences of developing and maintaining therapeutic alliances in stroke rehabilitation. A systematic literature search was conducted using the following electronic databases: PsycINFO, CINAHL, Embase, MEDLINE, Allied and Complementary Medicine Database, Applied Social Sciences Index and Abstracts, and ComDisDome from inception to May 2014. This was supplemented by hand searching, reference tracking, generic web searching, and e-mail contact with experts. Qualitative peer reviewed articles reporting experiences or perceptions of the patient or professional in relation to therapeutic alliance construction and maintenance in stroke rehabilitation were selected for inclusion. After a process of exclusion, 17 publications were included in the synthesis. All text identified in the results and discussion sections of the selected studies were extracted verbatim for analysis in a qualitative software program. Studies were critically appraised independently by 2 reviewers. Articles were synthesized using a technique of meta-ethnography. Four overarching themes emerged from the process of reciprocal translation: (1) the professional-patient relationship: degree of connectedness; (2) asymmetrical contributions; (3) the process of collaboration: finding the middle ground; and (4) system drivers. The findings from the meta-ethnography suggest that the balance of power between the patient and professional is asymmetrically distributed in the construction of the alliance. However, given that none of the studies included in the review addressed therapeutic alliance as a primary research area, further research is required to develop a conceptual framework relevant to stroke rehabilitation, in order to determine how this construct contributes to treatment efficacy. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  16. Therapeutic horticulture in clinical depression: a prospective study.

    Science.gov (United States)

    Gonzalez, Marianne Thorsen; Hartig, Terry; Patil, Grete Grindal; Martinsen, Egil W; Kirkevold, Marit

    2009-01-01

    Clinically depressed persons suffer from impaired mood and distortion of cognition. This study assessed changes in depression severity and perceived attentional capacity of clinically depressed adults (N=18) during a 12-week therapeutic horticulture program. The Beck Depression Inventory (BDI) and Attentional Function Index (AFI) were administered at baseline, twice during (4 and 8 weeks), and immediately after the intervention (12 weeks), and at a 3-month follow-up. Experiences of being away and fascination related to the intervention were measured at 4, 8, and 12 weeks. The mean BDI score declined 9.7 points from pretest (27.3) to posttest (p or =6) for 72% of the cases. The mean AFI score increased 10.2 points from pretest (68.8) to posttest (p = .06). The greatest change in BDI and AFI scores occurred in the initial weeks of the intervention. The reduction in BDI scores remained significant and clinically relevant at the 3-month follow-up (N=16). The decline in depression severity during the intervention correlated strongly with the degree to which the participants found that it captured their attention. Therapeutic horticulture may decrease depression severity and improve perceived attentional capacity by engaging effortless attention and interrupting rumination.

  17. Influence of FCGRT gene polymorphisms on pharmacokinetics of therapeutic antibodies.

    Science.gov (United States)

    Passot, Christophe; Azzopardi, Nicolas; Renault, Sylvaine; Baroukh, Nadine; Arnoult, Christophe; Ohresser, Marc; Boisdron-Celle, Michèle; Gamelin, Erick; Watier, Hervé; Paintaud, Gilles; Gouilleux-Gruart, Valérie

    2013-01-01

    The neonatal Fc receptor (FcRn) encoded by FCGRT is known to be involved in the pharmacokinetics (PK) of therapeutic monoclonal antibodies (mAbs). Variability in the expression of FCGRT gene and consequently in the FcRn protein level could explain differences in PK observed between patients treated with mAbs. We studied whether the previously described variable number tandem repeat (VNTR) or copy number variation (CNV) of FCGRT are associated with individual variations of PK parameters of cetuximab. VNTR and CNV were assessed on genomic DNA of 198 healthy individuals and of 94 patients treated with the therapeutic mAb. VNTR and CNV were analyzed by allele-specific PCR and duplex real-time PCR with Taqman (®) technology, respectively. The relationship between FCGRT polymorphisms (VNTR and CNV) and PK parameters of patients treated with cetuximab was studied. VNTR3 homozygote patients had a lower cetuximab distribution clearance than VNTR2/VNTR3 and VNTR3/VNTR4 patients (p = 0.021). We observed no affects of VNTR genotype on elimination clearance. One healthy person (0.5%) and 1 patient (1.1%) had 3 copies of FCGRT. The PK parameters of this patient did not differ from those of patients with 2 copies. The FCGRT promoter VNTR may influence mAbs' distribution in the body. CNV of FCGRT cannot be used as a relevant pharmacogenetic marker because of its low frequency.

  18. Polymer Therapeutics: Biomarkers and New Approaches for Personalized Cancer Treatment.

    Science.gov (United States)

    Atkinson, Stuart P; Andreu, Zoraida; Vicent, María J

    2018-01-23

    Polymer therapeutics (PTs) provides a potentially exciting approach for the treatment of many diseases by enhancing aqueous solubility and altering drug pharmacokinetics at both the whole organism and subcellular level leading to improved therapeutic outcomes. However, the failure of many polymer-drug conjugates in clinical trials suggests that we may need to stratify patients in order to match each patient to the right PT. In this concise review, we hope to assess potential PT-specific biomarkers for cancer treatment, with a focus on new studies, detection methods, new models and the opportunities this knowledge will bring for the development of novel PT-based anti-cancer strategies. We discuss the various "hurdles" that a given PT faces on its passage from the syringe to the tumor (and beyond), including the passage through the bloodstream, tumor targeting, tumor uptake and the intracellular release of the active agent. However, we also discuss other relevant concepts and new considerations in the field, which we hope will provide new insight into the possible applications of PT-related biomarkers.

  19. Carcinoma-Associated Fibroblasts Are a Promising Therapeutic Target

    International Nuclear Information System (INIS)

    Togo, Shinsaku; Polanska, Urszula M.; Horimoto, Yoshiya; Orimo, Akira

    2013-01-01

    Human carcinomas frequently exhibit significant stromal reactions such as the so-called “desmoplastic stroma” or “reactive stroma”, which is characterised by the existence of large numbers of stromal cells and extracellular matrix proteins. Carcinoma-associated fibroblasts (CAFs), which are rich in activated fibroblast populations exemplified by myofibroblasts, are among the predominant cell types present within the tumour-associated stroma. Increased numbers of stromal myofibroblasts are often associated with high-grade malignancies with poor prognoses in humans. CAF myofibroblasts possess abilities to promote primary tumour development, growth and progression by stimulating the processes of neoangiogenesis as well as tumour cell proliferation, survival, migration and invasion. Moreover, it has been demonstrated that CAFs serve as a niche supporting the metastatic colonisation of disseminated carcinoma cells in distant organs. Their contribution to primary and secondary malignancies makes these fibroblasts a potential therapeutic target and they also appear to be relevant to the development of drug resistance and tumour recurrence. This review summarises our current knowledge of tumour-promoting CAFs and discusses the therapeutic feasibility of targeting these cells as well as disrupting heterotypic interactions with other cell types in tumours that may improve the efficacy of current anti-tumour therapies

  20. Post-hemorrhagic hydrocephalus: Recent advances and new therapeutic insights.

    Science.gov (United States)

    Chen, Qianwei; Feng, Zhou; Tan, Qiang; Guo, Jing; Tang, Jun; Tan, Liang; Feng, Hua; Chen, Zhi

    2017-04-15

    Post-hemorrhagic hydrocephalus (PHH), also referred to as progressive ventricular dilatation, is caused by disturbances in cerebrospinal fluid (CSF) flow or absorption following hemorrhage in the brain. As one of the most serious complications of neonatal/adult intraventricular hemorrhage (IVH), subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI), PHH is associated with increased morbidity and disability of these events. Common sequelae of PHH include neurocognitive impairment, motor dysfunction, and growth impairment. Non-surgical measures to reduce increased intracranial pressure (ICP) in PHH have shown little success and most patients will ultimately require surgical management, such as external ventricular drainage and shunting which mostly by inserting a CSF drainage shunt. Unfortunately, shunt complications are common and the optimum time for intervention is unclear. To date, there remains no comprehensive strategy for PHH management and it becomes imperative that to explore new therapeutic targets and methods for PHH. Over past decades, increasing evidence have indicated that hemorrhage-derived blood and subsequent metabolic products may play a key role in the development of IVH-, SAH- and TBI-associated PHH. Several intervention strategies have recently been evaluated and cross-referenced. In this review, we summarized and discussed the common aspects of hydrocephalus following IVH, SAH and TBI, relevant experimental animal models, clinical translation of in vivo experiments, and potential preventive and therapeutic targets for PHH. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Polycystic Ovary Syndrome: Insights into the Therapeutic Approach with Inositols

    Science.gov (United States)

    Sortino, Maria A.; Salomone, Salvatore; Carruba, Michele O.; Drago, Filippo

    2017-01-01

    Polycystic ovary syndrome (PCOS) is characterized by hormonal abnormalities that cause menstrual irregularity and reduce ovulation rate and fertility, associated to insulin resistance. Myo-inositol (cis-1,2,3,5-trans-4,6-cyclohexanehexol, MI) and D-chiro-inositol (cis-1,2,4-trans-3,5,6-cyclohexanehexol, DCI) represent promising treatments for PCOS, having shown some therapeutic benefits without substantial side effects. Because the use of inositols for treating PCOS is widespread, a deep understanding of this treatment option is needed, both in terms of potential mechanisms and efficacy. This review summarizes the current knowledge on the biological effects of MI and DCI and the results obtained from relevant intervention studies with inositols in PCOS. Based on the published results, both MI and DCI represent potential valid therapeutic approaches for the treatment of insulin resistance and its associated metabolic and reproductive disorders, such as those occurring in women affected by PCOS. Furthermore, the combination MI/DCI seems also effective and might be even superior to either inositol species alone. However, based on available data, a particular MI:DCI ratio to be administered to PCOS patients cannot be established. Further studies are then necessary to understand the real contents of MI or DCI uptaken by the ovary following oral administration in order to identify optimal doses and/or combination ratios. PMID:28642705

  2. Neurotransmitter regulation of adult neurogenesis: putative therapeutic targets.

    Science.gov (United States)

    Vaidya, V A; Vadodaria, K C; Jha, S

    2007-10-01

    The evidence that new neuron addition takes place in the mammalian brain throughout adult life has dramatically altered our perspective of the potential for plasticity in the adult CNS. Although several recent reports suggest a latent neurogenic capacity in multiple brain regions, the two major neurogenic niches that retain the ability to generate substantial numbers of new neurons in adult life are the subventricular zone (SVZ) lining the lateral ventricles and the subgranular zone (SGZ) in the hippocampal formation. The discovery of adult neurogenesis has also unveiled a novel therapeutic target for the repair of damaged neuronal circuits. In this regard, understanding the endogenous mechanisms that regulate adult neurogenesis holds promise both for a deeper understanding of this form of structural plasticity, as well as the identification of pathways that can serve as therapeutic targets to manipulate adult neurogenesis. The purpose of the present review is to discuss the regulation of adult neurogenesis by neurotransmitters and to highlight the relevance of these endogenous regulators as targets to modulate adult neurogenesis in a clinical context.

  3. Underscreening in concentrated electrolytes.

    Science.gov (United States)

    Lee, Alpha A; Perez-Martinez, Carla S; Smith, Alexander M; Perkin, Susan

    2017-07-01

    Screening of a surface charge by an electrolyte and the resulting interaction energy between charged objects is of fundamental importance in scenarios from bio-molecular interactions to energy storage. The conventional wisdom is that the interaction energy decays exponentially with object separation and the decay length is a decreasing function of ion concentration; the interaction is thus negligible in a concentrated electrolyte. Contrary to this conventional wisdom, we have shown by surface force measurements that the decay length is an increasing function of ion concentration and Bjerrum length for concentrated electrolytes. In this paper we report surface force measurements to test directly the scaling of the screening length with Bjerrum length. Furthermore, we identify a relationship between the concentration dependence of this screening length and empirical measurements of activity coefficient and differential capacitance. The dependence of the screening length on the ion concentration and the Bjerrum length can be explained by a simple scaling conjecture based on the physical intuition that solvent molecules, rather than ions, are charge carriers in a concentrated electrolyte.

  4. Angiogenesis and vascular targeting: Relevance for hyperthermia

    DEFF Research Database (Denmark)

    Horsman, Michael R

    2008-01-01

    The creation of a functional blood supply from the normal tissue vasculature via the process of angiogenesis is critical for the continued growth and development of solid tumours. This importance has led to the concept of targeting the tumour vasculature as a therapeutic strategy, and two major...... types of vascular targeting agents (VTAs) have developed; those that inhibit the angiogenic process-angiogenesis inhibiting agents (AIAs)-and those that specifically damage the already established neovasculature-vascular disrupting agents (VDAs). The tumour vasculature also plays a critical role...

  5. [Incidence and follow-up characteristics of neurologically relevant psychogenic symptoms].

    Science.gov (United States)

    Franz, M; Schellberg, D; Reister, G; Schepank, H

    1993-06-01

    The author reports on the prevalence and stability of the course of neurologically relevant psychogenic symptoms as well as their dependence on age and sex. Altogether 240 probands from the Mannheim Cohort Study on the epidemiology of psychogenic disorders were examined for psychogenic impairment over a 10-year period during three investigation periods. On the whole, seven neurologically relevant groups of symptoms (headache, lumbar and cervical vertebral complaints, non-systematic vertigo, functional hyperkinesia, functional paresis, sleep disturbances, concentration disturbances) differ clearly in frequency, characteristics of the course and clinical relevance.

  6. Concentrating photovoltaic solar panel

    Science.gov (United States)

    Cashion, Steven A; Bowser, Michael R; Farrelly, Mark B; Hines, Braden E; Holmes, Howard C; Johnson, Jr., Richard L; Russell, Richard J; Turk, Michael F

    2014-04-15

    The present invention relates to photovoltaic power systems, photovoltaic concentrator modules, and related methods. In particular, the present invention features concentrator modules having interior points of attachment for an articulating mechanism and/or an articulating mechanism that has a unique arrangement of chassis members so as to isolate bending, etc. from being transferred among the chassis members. The present invention also features adjustable solar panel mounting features and/or mounting features with two or more degrees of freedom. The present invention also features a mechanical fastener for secondary optics in a concentrator module.

  7. Too much of a good thing: a retrospective study of β-lactam concentration-toxicity relationships.

    Science.gov (United States)

    Imani, Sahand; Buscher, Hergen; Marriott, Debbie; Gentili, Sheridan; Sandaradura, Indy

    2017-10-01

    To determine the existence of concentration-toxicity relationships for common β-lactam antibiotic adverse effects and define thresholds above which toxicity is more likely. Retrospective review of consecutive patients treated with piperacillin, meropenem or flucloxacillin who underwent therapeutic drug monitoring (TDM) at St Vincent's Hospital (Sydney, Australia) between January 2013 and December 2015. Adverse events investigated included neurotoxicity, nephrotoxicity, hepatotoxicity and opportunistic Clostridium difficile infection. Toxicity was measured using observational grading criteria, clinical assessment and relevant serum biomarkers. These findings were correlated with trough TDM measurements at the time of toxicity presentation. TDM results from 378 patients (piperacillin = 223, meropenem = 94 and flucloxacillin = 61) were investigated. There was no difference in baseline patient characteristics across antibiotic groups. A statistically significant elevation in mean serum trough concentrations (Cmin) was found in patients diagnosed with neurotoxicity (piperacillin, P 361.4 mg/L; meropenem, Cmin >64.2 mg/L; flucloxacillin, Cmin >125.1 mg/L) or nephrotoxicity (piperacillin, Cmin >452.65 mg/L; meropenem, Cmin >44.45 mg/L) varied across antibiotics. Our data reveal an association between toxic concentrations for a number of β-lactam agents and neurotoxic/nephrotoxic effects. We have defined threshold concentrations above which these toxicities become more likely. Clinicians should balance concerns for therapeutic efficacy with potential toxicity when considering aggressive therapy. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Selection of antibiotic resistance at very low antibiotic concentrations

    OpenAIRE

    Sandegren, Linus

    2014-01-01

    Human use of antibiotics has driven the selective enrichment of pathogenic bacteria resistant to clinically used drugs. Traditionally, the selection of resistance has been considered to occur mainly at high, therapeutic levels of antibiotics, but we are now beginning to understand better the importance of selection of resistance at low levels of antibiotics. The concentration of an antibiotic varies in different body compartments during treatment, and low concentrations of antibiotics are fou...

  9. Exposure-Relevant Ozone Chemistry in Occupied Spaces

    Energy Technology Data Exchange (ETDEWEB)

    Coleman, Beverly Kaye [Univ. of California, Berkeley, CA (United States)

    2009-04-01

    Ozone, an ambient pollutant, is transformed into other airborne pollutants in the indoor environment. In this dissertation, the type and amount of byproducts that result from ozone reactions with common indoor surfaces, surface residues, and vapors were determined, pollutant concentrations were related to occupant exposure, and frameworks were developed to predict byproduct concentrations under various indoor conditions. In Chapter 2, an analysis is presented of secondary organic aerosol formation from the reaction of ozone with gas-phase, terpene-containing consumer products in small chamber experiments under conditions relevant for residential and commercial buildings. The full particle size distribution was continuously monitored, and ultrafine and fine particle concentrations were in the range of 10 to>300 mu g m-3. Particle nucleation and growth dynamics were characterized.Chapter 3 presents an investigation of ozone reactions with aircraft cabin surfaces including carpet, seat fabric, plastics, and laundered and worn clothing fabric. Small chamber experiments were used to determine ozone deposition velocities, ozone reaction probabilities, byproduct emission rates, and byproduct yields for each surface category. The most commonly detected byproducts included C1?C10 saturated aldehydes and skin oil oxidation products. For all materials, emission rates were higher with ozone than without. Experimental results were used to predict byproduct exposure in the cabin and compare to other environments. Byproduct levels are predicted to be similar to ozone levels in the cabin, which have been found to be tens to low hundreds of ppb in the absence of an ozone converter. In Chapter 4, a model is presented that predicts ozone uptake by and byproduct emission from residual chemicals on surfaces. The effects of input parameters (residue surface concentration, ozone concentration, reactivity of the residue and the surface, near-surface airflow conditions, and

  10. Photovoltaic static concentrator analysis

    Science.gov (United States)

    Almonacid, G.; Luque, A.; Molledo, A. G.

    1984-12-01

    Ray tracing is the basis of the present analysis of truncated bifacial compound parabolic concentrators filled with a dielectric substance, which are of interest in photovoltaic applications where the bifacial cells allow higher static concentrations to be achieved. Among the figures of merit for this type of concentrator, the directional intercept factor plays a major role and is defined as the ratio of the power of the collector to that at the entry aperture, in a lossless concentrator illuminated by light arriving from a given direction. A procedure for measuring outdoor, full size panels has been developed, and a correction method for avoiding the effect of unwanted diffuse radiation during the measurements is presented.

  11. CMAQ predicted concentration files

    Data.gov (United States)

    U.S. Environmental Protection Agency — model predicted concentrations. This dataset is associated with the following publication: Muñiz-Unamunzaga, M., R. Borge, G. Sarwar, B. Gantt, D. de la Paz, C....

  12. Vaginal oxytetracycline concentrations.

    Science.gov (United States)

    Thin, R N; Al Rawi, Z H; Simmons, P D; Treharne, J; Tabaqchali, S

    1979-01-01

    Although tetracycline preparations are widely used in departments of genitourinary medicine, or sexually transmitted diseases clinics, little is known of the concentrations of these preparations in genital secretions. For this reason a microbiological method was used for estimating oxytetracycline concentrations in vaginal secretions. These concentrations varied from 0.6 to 6.5 microgram/ml in 19 women who had had sexual contact with a man with non-specific urethritis and who were taking oxytetracycline dihydrate 250 mg four times daily. They were well in excess of the minimum inhibitory concentration of oxytetracycline (0.2 microgram/ml) for the strains of Chlamydia trachomatis isolated from the patients with positive culture results. Thus, oxytetracycline 250 mg four times daily appears to be a satisfactory regimen for the treatment of chlamydial genital infection in women. PMID:509190

  13. Concentrations of Indicator Organisms

    Data.gov (United States)

    U.S. Environmental Protection Agency — It is a compilation of organism concentrations of 16 sampling events conducted between July 2015 and February 2016. It also includes statistical analysis such as...

  14. Concentrated Differential Privacy

    OpenAIRE

    Dwork, Cynthia; Rothblum, Guy N.

    2016-01-01

    We introduce Concentrated Differential Privacy, a relaxation of Differential Privacy enjoying better accuracy than both pure differential privacy and its popular "(epsilon,delta)" relaxation without compromising on cumulative privacy loss over multiple computations.

  15. Relevance of Fusion Genes in Pediatric Cancers: Toward Precision Medicine

    Directory of Open Access Journals (Sweden)

    Célia Dupain

    2017-03-01

    Full Text Available Pediatric cancers differ from adult tumors, especially by their very low mutational rate. Therefore, their etiology could be explained in part by other oncogenic mechanisms such as chromosomal rearrangements, supporting the possible implication of fusion genes in the development of pediatric cancers. Fusion genes result from chromosomal rearrangements leading to the juxtaposition of two genes. Consequently, an abnormal activation of one or both genes is observed. The detection of fusion genes has generated great interest in basic cancer research and in the clinical setting, since these genes can lead to better comprehension of the biological mechanisms of tumorigenesis and they can also be used as therapeutic targets and diagnostic or prognostic biomarkers. In this review, we discuss the molecular mechanisms of fusion genes and their particularities in pediatric cancers, as well as their relevance in murine models and in the clinical setting. We also point out the difficulties encountered in the discovery of fusion genes. Finally, we discuss future perspectives and priorities for finding new innovative therapies in childhood cancer.

  16. Industrialisation et concentration urbaine

    OpenAIRE

    Kamal , Abdelhak

    2010-01-01

    The aim of this thesis is to analyze the determinants of the urban concentration and their effect at different levels of development. The empirical analysis focuses on the developing countries over the period 1950-2000 grouped by level of per capita income. The results confirm the existence of specific trajectories of urbanization rate and urban primacy which differs meaningfully according to the stage of development considered. Certain factors encourage urbanization and its concentration in ...

  17. Solar concentrators. Concentradores solares

    Energy Technology Data Exchange (ETDEWEB)

    Almanza, R.; Valdes, A.; Lopez, S.

    1981-06-01

    This paper presents different types of geometries used in concentrators. Some comments are made on the theoretical and experimental analysis necessary to evaluate the geometries and on the type of laboratory equipment needed to obtain experimental data. At the end of the report a description of how to build parabolic trough mirrors is made. The experience gained by the authors, who have been working in this subject for the past five years, is summarized, showing some of the problems related with such concentrators.

  18. Concentration factors for fish

    International Nuclear Information System (INIS)

    Feldt, W.; Lauer, R.; Melzer, M.; Siebert, W.

    1978-01-01

    Concentration factors are defined as operators allowing to calculate the specific activity of fish meat from a given concentration of an element in the water. This parameter depends among others from the content of stable isotopes and homologues in the different waters. If this parameter is reasonably to be used for model calculations it must be referred to water with all of its content substances, these calculations also being based on this type of 'water'. (orig.) [de

  19. FK concentrator outdoor measurements

    OpenAIRE

    Hernández Sanz, Maikel; Vilaplana, J., J.; Benitez Gimenez, Pablo; Mohedano,, Rubén; Zamora Herranz, Pablo; Miñano Dominguez, Juan Carlos; Mendes Lopes, Joao

    2013-01-01

    The FK is a two-stage optical concentrator for CPV, composed by a Fresnel lens working as POE and a refractive element working as SOE. Both elements perform Köhler integration, for uniform irradiance purposes. The FK has demonstrated that compares very well with other Fresnel-based concentrator optics. Recent on-sun measurements carried out on an FK mono-module prototype have already shown outstanding results, achieving electrical efficiencies over 34%. Further optimization of optical design ...

  20. A rational quantitative approach to determine the best dosing regimen for a target therapeutic effect: a unified formalism for antibiotic evaluation.

    Science.gov (United States)

    Li, Jun; Nekka, Fahima

    2013-02-21

    The determination of an optimal dosing regimen is a critical step to enhance the drug efficacy and avoid toxicity. Rational dosing recommendations based on mathematical considerations are increasingly being adopted in the process of drug development and use. In this paper, we propose a quantitative approach to evaluate the efficacy of antibiotic agents. By integrating both pharmacokinetic (PK) and pharmacodynamic (PD) information, this approach gives rise to a unified formalism able to measure the cause-effect of dosing regimens. This new pharmaco-metric allows to cover a whole range of antibiotics, including the two well known concentration and time dependent classes, through the introduction of the Hill-dependency concept. As a direct fallout, our formalism opens a new path toward the bioequivalence evaluation in terms of PK and PD, which associates the in vivo drug concentration and the in vitro drug effect. Using this new approach, we succeeded to reveal unexpected, but relevant behaviors of drug performance when different drug regimens and drug classes are considered. Of particular notice, we found that the doses required to reach the same therapeutic effect, when scheduled differently, exhibit completely different tendencies for concentration and time dependent drugs. Moreover, we theoretically confirmed the previous experimental results of the superiority of the once daily regimen of aminoglycosides. The proposed methodology is appealing for its computational features and can easily be applicable to design fair clinical protocols or rationalize prescription decisions. Copyright © 2012 Elsevier Ltd. All rights reserved.